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review_id (string)pmid (sequence)title (sequence)abstract (sequence)target (string)
"CD007697"
[ "16394043" ]
[ "Aggressive surgical effort and improved survival in advanced-stage ovarian cancer." ]
[ "Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival.\n A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival.\n The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001).\n Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis.\n II-2." ]
"We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival.  It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery. In order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required."
"CD000174"
[ "8627434", "2677294", "3373404", "3321891", "8201485", "11430325", "3373405", "3174314", "9078828", "3312552", "3906073", "1305392", "3998921", "10730525" ]
[ "Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.", "Indomethacin reduces the risks of severe intraventricular hemorrhage.", "Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates.", "Early intravenous indomethacin prolongs respiratory support in very low birth weight infants.", "Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial.", "Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.", "Randomized low-dose indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight neonates.", "Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants.", "Effects of early indomethacin administration on oxygenation and surfactant requirement in low birth weight infants.", "Prevention of symptomatic patent ductus arteriosus with a single dose of indomethacin.", "Randomized indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight infants.", "[Indomethacin in the prevention of subependymal-intraventricular hemorrhage in preterm newborns with conventional mechanical ventilation].", "Indomethacin therapy on the first day of life in infants with very low birth weight.", "Indomethacin prophylaxis for patent ductus arteriosus (PDA) in infants with a birth weight of less than 1250 grams." ]
[ "To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room.\n Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation.\n Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis.\n The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.", "A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.", "One hundred twenty-two preterm infants were enrolled in a placebo-controlled, double-blind trial using intravenous indomethacin for the prevention of periventricular-intraventricular hemorrhage (PVH-IVH). Before random assignment, data on the infants were stratified according to low-weight (500 to 999 g) or high-weight (1000 to 1500 g) subgroups. Cranial sonography was used to document the absence of PVH-IVH before enrollment and the occurrence of PVH-IVH during the 7-day protocol. Indomethacin, 0.1 mg/kg, or placebo was administered before 12 hours of age and at 24, 48, and 72 hours of age. Five patients receiving indomethacin and six receiving placebo were withdrawn before completion of the study. In the remaining 111 patients, the indomethacin and placebo groups were comparable with respect to gestational ages, maternal complications, Apgar scores, ventilatory requirements, complications of prematurity, and mortality rate. PVH-IVH developed in six of 56 infants who received indomethacin and 11 of 55 infants who received placebo (P = 0.174). Analysis of the individual strata showed that the indomethacin-treated infants in the low-weight subgroup sustained a higher mortality rate (11/17 vs 3/16; P = 0.008) without a reduction in the incidence of PVH-IVH. Infants in the indomethacin-treated high-weight subgroup demonstrated a significantly lower incidence of PVH-IVH (2/39 vs 8/39; P = 0.04), but the frequency of high-grade hemorrhages was comparable for both indomethacin- and placebo-treated groups. In summary, the prophylactic administration of intravenous indomethacin for the prevention of PVH-IVH cannot be recommended for infants less than 1000 g. In preterm infants between 1000 and 1500 g birth weight, indomethacin significantly reduced the incidence of PVH-IVH.", "Infants weighing 1500 g at birth requiring either intermittent positive pressure ventilation or continuous positive airway pressure by 12 hours of age were entered in a randomized double blind controlled trial to test the efficacy of early intravenous indomethacin therapy in preventing chronic pulmonary disease of prematurity. Of the 30 newborns enrolled, 15 were treated with indomethacin and 15 were treated with placebo at 12, 24 and 36 hours of age. The groups were similar for birth weight, gestational age, sex, hyaline membrane disease and intracranial hemorrhage. Infants in the placebo group were successfully weaned from intermittent positive pressure ventilation at an earlier age than infants in the indomethacin group (p less than 0.05). Furthermore, chronic pulmonary disease of prematurity was similar in the two groups despite a reduction in the incidence of patent ductus arteriosus in the indomethacin group.", "We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin-treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage.", "The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known.\n Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy.\n Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin.\n In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.", "We admitted 36 preterm neonates (600 to 1250 gm birth weight) with normal 6-hour echoencephalograms to a randomized, placebo-controlled prospective trial to determine whether a low dose of indomethacin would prevent germinal matrix or intraventricular hemorrhage and permit adequate urinary output. Between the sixth and tenth postnatal hours, indomethacin (0.1 mg/kg) or placebo was administered intravenously every 24 hours for a total of three doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, serum indomethacin levels, and renal and clotting functions were monitored. No differences in birth weight, gestational age, or Apgar scores were noted between the two groups of infants. Two indomethacin-treated infants and three infants given placebo had significant urinary output difficulties, requiring that the study medication be withheld. Of 19 infants given indomethacin, two had germinal matrix or intraventricular hemorrhage, in comparison with 8 of 17 infants given saline solution (p = 0.02). Of the infants who had a left-to-right patent ductus arteriosus shunt before treatment, 64% of the indomethacin-treated and 33% of the saline solution-treated infants no longer had a patent ductus arteriosus on day 5. Ductal status appeared unrelated to the development of germinal matrix or intraventricular hemorrhage.", "The impact of early prophylactic use of intravenous indomethacin on the incidence and severity of periventricular-intraventricular hemorrhage and patent ductus arteriosus in 199 oxygen-requiring premature infants (less than or equal to 1300 g birth weight) was prospectively investigated. The trial was controlled, the infants were randomized, and the investigators were unaware of the group assignments. Patients with minimal (grade I) or no periventricular-intraventricular hemorrhage determined by prestudy echoencephalography were randomized within two birth weight subgroups (500 to 899 and 900 to 1300 g) to receive either prophylactic indomethacin (n = 99) or an equal volume of saline-vehicle placebo (n = 100). The first dose (0.2 mg/kg) was given within 12 hours of delivery and two subsequent doses (0.1 mg/kg) were administered at 12 hourly intervals. Prophylactic indomethacin significantly reduced the incidence of grades II to IV periventricular-intraventricular hemorrhage. Intraventricular hemorrhage was half as common in infants given prophylactic indomethacin as in control infants (23% v 46%, P less than .002). The reduction was manifested in both birth weight subgroups. Results of this study also confirmed a lower incidence of clinically significant patent ductus arteriosus in infants who received prophylactic indomethacin in contrast to those who received placebo (11% v 42%, P less than .001). No significant differences were found between treatment and control groups in the duration of oxygen therapy, mechanical ventilation, or hospitalization or in the incidence of pneumothorax, chronic lung disease, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Early prophylactic indomethacin initiated within 12 hours of delivery is effective in reducing the incidence of intraventricular hemorrhage as well as clinically significant patent ductus arteriosus in very low birth weight premature infants.", "A previous study found that early intravenous indomethacin administration prolonged respiratory support in very low birth weight infants. We have, therefore, designed a randomized, double blind controlled study to evaluate the oxygenation, and surfactant requirements in preterm low birth weight infants receiving early indomethacin administration. Premature neonates who received surfactant therapy and on mechanical ventilation were prospectively randomized to receive either placebo or indomethacin (0.2 mg/kg intravenously at 12 postnatal hours and every 24 h for two more doses). Oxygenation was assessed by FiO2 required and arterial/alveolar oxygen (a/A O2) ratio during the first 48 h of life. The doses of surfactant were compared between the two groups. Twenty-seven infants (n = 14 of early indomethacin and n = 13 of placebo group) fulfilled inclusion criteria. At admission to the study, there were no differences in the birth weight, gestational age, sex, Apgar scores, a/A O2 ratio, and FiO2. The control group exhibited a significant improvement in oxygenation (FiO2 requirement and a/A O2 compared with the early indomethacin group at 24 (P = 0.026 and 0.02, respectively) and 48 h of life (P = 0.037 and 0.026, respectively). The requirement of surfactant was significantly larger in the early indomethacin group (P = 0.029). Early indomethacin administration increases oxygen and surfactant requirement.", "To determine the efficacy of indomethacin to prevent the occurrence of symptomatic patent ductus arteriosus (PDA), a randomized clinical trial was conducted involving 32 preterm infants weighing 750 to 1500 g at birth who had hyaline membrane disease. By random assignment, 15 infants were given a single dose of indomethacin, 0.2 mg/kg intravenously, 24 hours after birth. Seventeen infants composed a control group for which indomethacin was reserved as treatment for symptomatic PDA. Birth weight, gestational age, male/female ratio, black/white ratio, and severity of disease were similar for both groups. Only one of the 14 survivors who received prophylactic indomethacin had symptomatic PDA, compared with nine of the 16 survivors in the control group (P = 0.007). There was no difference between the groups in development of bronchopulmonary dysplasia, duration of time endotracheal intubation, was required, duration in oxygen, duration to reach full feedings and regain birth weight, and duration of hospital stay. There was no difference between the two groups in incidence of intraventricular hemorrhage, and none developed necrotizing enterocolitis. These results indicate that the use of prophylactic indomethacin is beneficial in prevention of symptomatic PDA; the lack of differences in pulmonary sequelae or other complications may have been related to a population sample size not large enough to impart sufficient statistical power.", "We admitted 48 preterm neonates (600 to 1250 gm birth weight, normal 6-hour echoencephalograms) to a randomized prospective indomethacin or placebo trial for the prevention of neonatal intraventricular hemorrhage. Beginning at 6 postnatal hours, indomethacin or placebo was administered intravenously every 12 hours for a total of five doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, and renal and clotting functions were monitored. No differences in birth weight, gestational age, Apgar scores, or ventilatory needs were noted between the two groups. Six infants given indomethacin had intraventricular hemorrhage, compared to 14 control infants (P = 0.02). The indomethacin-treated group had significant decreases in serum prostaglandin values 30 hours after the initiation of therapy. The overall incidence of patent ductus arteriosus was 82% at 6 postnatal hours; 84% of the indomethacin-treated infants experienced closure of the ductus, compared to 60% of the placebo-treated patients. Closure of the ductus was not related to incidence of intraventricular hemorrhage. We speculate that indomethacin may provide some protection against neonatal intraventricular hemorrhage by acting on the cerebral microvasculature.", "The results of a double blind study to evaluate the efficiency of prophylactic endovenous indomethacin versus placebo for prevention of intraventricular hemorrhage (IVH) in newborn infants between 28 to 36 weeks of age who were intubated at the delivery room and required mechanical ventilation in NICU are presented. Fourty six patients required mechanical ventilation, but 14 neonates had IVH evaluated by ultrasound when were admitted to the Unit. At least 32 infants were studied, 16 for each group. There were no differences between the groups in weight, gestational age, sex and delivery way. The mobility was the same in relation to hialine membrane disease, sepsis, pneumonie and pneumotorax. The placebo group had more frequency of PDA and mortality (P < 0.5). There were no differences in mean airway pressure and arterial gases, also in glucose, platelets and urinary volume. The indomethacin group had mayor urinary density and FeNa but the results were always in normal ranges. The IVH was the same in both groups. We concluded that the indomethacin at the levels used did not produced alterations, and if the IVH is not prevented, were observed lesser severity of the same and the frequency of PDA and mortality are lesser. But still is necessary more number of cases for best conclusions.", "To investigate the optimal timing for treatment of small premature infants, we performed a double-blind, controlled trial of indomethacin therapy on the first day of life in 104 infants weighing between 700 and 1300 gm. Infants were given indomethacin or placebo at a mean age of 15 hours. Eleven of the 56 infants given placebo developed large left-to-right shunts through a patent ductus arteriosus. In contrast, only two of the 51 infants given indomethacin developed large shunts (P less than 0.025). There were no significant differences in incidence of surgical ligation, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight, or incidence of complications. However, the power of the tests of significance was low because of the small number of patients. Thus, although the incidence of large left-to-right ductus shunts was decreased in the indomethacin group, morbidity was not otherwise altered for the entire group of patients, possibly because of the relatively low incidence (21%) of large shunts in the placebo group. We conclude that although treatment with indomethacin on the first day of life appears to be safe, there is little advantage to its use in centers where the incidence of large shunts through a patent ductus arteriosus is relatively low.", "Very low birth weight (VLBW, less than 1500 g) and extremely low birth weight infants (ELBW, less than 1000 g) are the premature infants that are most likely to develop symptomatic PDA. Intravenous indomethacin has proven effective in prevention of PDA in many prospective trials. This strategy will be a useful adjunctive therapy for premature infants in Thailand.\n To answer the following questions: 1. Will multiple doses of intravenous indomethacin, given to VLBW infants within the first day of life, effectively prevent the occurrence of symptomatic PDA? Are there any side effects or complications? 2. Will this strategy be more beneficial in ELBW?\n The study included thirty VLBW infants born at Ramathibodi Hospital, with birth weights ranging from 630 to 1230 g. They were randomized into 2 groups of 15 infants each. One group received 3 doses of intravenous indomethacin at the dosage of 0.2 mg/kg initially and then 0.1 mg/kg every 12 hours for 2 more doses; the second group received a placebo. The study was performed by a double blind control.\n Sixteen infants developed symptomatic PDA, 4 in the indomethacin group and 12 in the placebo group. The decrease in incidence of PDA is statistically significant. But when the data was analyzed separately for the VLBW and ELBW groups. The effects were only significantly different in ELBW but not yet significant in the VLBW group. There was a statistically significant difference in the incidence of severe intraventricular hemorrhage (IVH) (grade 3 or higher) in the ELBW infants.\n Intravenous indomethacin therapy given to VLBW infants with a birth weight of less than 1250 g decreased incidence of symptomatic PDA with no significant permanent side effects. The effect was markedly noticeable in ELBW infants. Incidence of severe IVH was also markedly decreased in the ELBW infants who received indomethacin." ]
"Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment."
"CD008805"
[ "6024144", "4915981" ]
[ "White phosphorus burns and massive hemolysis.", "The treatment of chemical burns: specialized diagnostic, therapeutic, and prognostic considerations." ]
[ "nan", "nan" ]
"First aid for phosphorus burns involves the common sense measures of acting promptly to remove the patient's clothes, irrigating the wound(s) with water or saline continuously, and removing phosphorus particles. There is no evidence that using copper sulphate to assist visualisation of phosphorus particles for removal is associated with better outcome, and some evidence that systemic absorption of copper sulphate may be harmful. We have so far been unable to identify any other comparisons relevant to informing other aspects of the care of patients with phosphorus burns. Future versions of this review will take account of information in articles published in languages other than English, which may contain additional evidence based on treatment comparisons."
"CD000248"
[ "1159434", "14168625", "13969171", "14250709" ]
[ "Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.", "CEREBRAL VASCULAR DISEASE IN RELATION TO LONG-TERM ANTICOAGULANT THERAPY.", "Anticoagulant therapy in cerebral infarction. Report on cooperative study.", "CEREBRAL APOPLEXY. A CLINICAL, RADIOLOGICAL, ELECTROENCEPHALOGRAPHIC AND PATHOLOGICAL STUDY WITH SPECIAL REFERENCE TO THE PROGNOSIS OF CEREBRAL INFARCTION AND THE RESULT OF LONG-TERM ANTICOAGULATION THERAPY." ]
[ "The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.", "nan", "nan", "nan" ]
"Compared with control, there was no evidence of benefit from long-term anticoagulant therapy in people with presumed non-cardioembolic ischaemic stroke or transient ischaemic attack, but there was a significant bleeding risk."
"CD004431"
[ "15240203", "11212135", "6487909", "3693660", "12690582", "11784832", "12883103", "4074113", "10780138", "11777121", "11527284", "8116338", "12583502" ]
[ "Computer-aided retraining of memory and attention in people with multiple sclerosis: a randomized, double-blind controlled trial.", "Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.", "An evaluation of cognitive-behaviour therapy for depression in patients with multiple sclerosis.", "Efficacy of stress-inoculation training in coping with multiple sclerosis.", "A randomized clinical trial of a wellness intervention for women with multiple sclerosis.", "Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.", "Effects of treatment for depression on fatigue in multiple sclerosis.", "Group psychotherapy: benefits in multiple sclerosis.", "Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis.", "Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.", "Unit management of depression of patients with multiple sclerosis using cognitive remediation strategies: a preliminary study.", "Effects of neuropsychological treatment in patients with multiple sclerosis.", "Symptom management and adjustment of patients with multiple sclerosis: a 4-year longitudinal intervention study." ]
[ "Cognitive compromise is one of the main contributing factors to activity and participation restrictions in people with multiple sclerosis (MS). Computer-aided programs are used for retraining memory and attention, but data on the efficacy of these interventions are scarce.\n To assess the efficacy of computer-aided retraining of memory and attention in people with MS impaired in these abilities.\n Randomized, double-blind, controlled trial.\n Outpatients (n=82) with subjective complaints of poor attention or memory, confirmed by a score <80th percentile in at least two tests of the Brief Repeatable Battery of Neuropsychological Tests (BRBNT).\n Participants were randomized to two computer-assisted retraining interventions: memory and attention (study arm), and visuo-constructional and visuo-motor coordination (control arm). Both groups received 16 training sessions over 8 weeks.\n Improvement of 20% or more in at least two BRBNT test scores at 8 weeks compared to baseline (primary end point). Changes in depression and health-related quality of life.\n An improvement occurred in 45% of study patients vs. 43% of control patients (odds ratio 1.07, 95% confidence interval 0.44-2.64). The study treatment was better than the control treatment only on the word list generation test (p=0.016).\n This trial does not support the efficacy of specific memory and attention retraining in MS.", "We studied the effectiveness of a newly-developed cognitive-behavioral intervention in 15 patients with marked cognitive impairment and behavior disorder. The design was a single-blind test of a neuropsychological intervention, with pre- and post-treatment assessments of personality and social behavior. MS patients underwent neurological examination and neuropsychological testing at baseline. The patients were then randomly assigned to neuropsychological counseling or standard, non-specific supportive psychotherapy. The active 12-week treatment emphasized enhancement of insight through education, social skills training, and behavior modification. All patients were re-examined within 2 weeks of the termination of treatment. Neuropsychological technicians were blind to treatment condition. Both groups showed evidence of cognitive impairment and personality/behavior disorder prior to treatment and were well matched on demographic, disability, and cognitive measures. Patients who underwent neuropsychological counseling showed significant positive response on measures of social behavior (e.g. excessive ego-centric speech) compared to those who underwent standard counseling. We conclude that these data support the use of non-pharmacological, neuropsychological counseling in patients with acquired, MS-associated behavior disorder.", "Twenty depressed multiple sclerotic patients were randomly allocated either to cognitive-behaviour therapy or to a waiting list control condition. Assessment of depressive symptoms was conducted at pre-treatment, post-treatment, and a four-week follow-up. In comparison to the waiting list condition, cognitive-behaviour therapy was found to result in clinically and statistically significant improvement on most measures. Although the mechanism by which such treatment achieves its effects is unclear, these results clearly support the use of cognitive-behavioural treatments for depression in this population.", "nan", "To examine the effects of a wellness intervention program for women with multiple sclerosis (MS) on health behaviors and quality of life (QOL).\n Randomized clinical trial.\n Community setting in the southwestern United States.\n Convenience sample of 113 women with physician-confirmed MS (mean age, 45.79y).\n The 2-phase intervention program included lifestyle-change classes for 8 weeks, then telephone follow-up for 3 months. Participants were followed over an 8-month period.\n A series of self-report instruments to measure barriers, resources, self-efficacy for health behaviors, health promotion behaviors, and health-related QOL were completed at baseline, 2 months (after the classes), 5 months (after telephone follow-up), and at 8 months. Principal outcomes measures were health-promoting behaviors (scores on the Health Promoting Lifestyle Profile II) and QOL (scores on the Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36] scales).\n Hierarchical linear modeling techniques revealed a statistically significant group by time effect for self-efficacy for health behaviors, health-promoting behaviors, and the mental health and pain scales of the SF-36.\n These data provide initial support for the positive effects of wellness interventions to improve health behaviors and selected dimensions of QOL for women with MS.", "Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis.\n The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire.\n The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence.\n The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis.", "There has long been a belief that depression contributes to fatigue in multiple sclerosis (MS) although supporting data are minimal at best. Clinical guidelines for the treatment of fatigue include recommendations for the treatment of depression in the absence of clear empirical support. The goal of this study was to examine the effects of treatment for depression on fatigue in MS.\n Sixty patients with a relapsing form of MS and moderate to severe depression were randomly assigned to one of three validated 16-week treatments for depression: individual cognitive behavioral therapy, group psychotherapy, or sertraline. Assessments at baseline and treatment cessation included the primary outcome measure, fatigue assessment instrument (FAI), and Beck depression inventory (BDI).\n The total FAI and the global fatigue severity subscale were significantly reduced over the course of treatment (p values <.02). Other subscales did not change significantly. Secondary analyses showed change in global fatigue severity was associated with change in BDI (p =.03) but change in total FAI was only marginally related to change in BDI (p =.05). These relationships were due entirely to change in mood (p values <.02) and not to change in cognitive or vegetative symptoms (p values >.17).\n These findings suggest that treatment for depression is associated with reductions in the severity of fatigue symptoms, and that this relationship is due primarily to treatment related changes in mood.", "This study investigates the relationship between group psychotherapy and the psychologic adjustment of patients with a primary diagnosis of multiple sclerosis (MS). It was speculated that such a program would decrease both patient depression and anxiety, at the same time increasing self-concept and self-direction. Forty-one hospitalized MS patients were screened for mental status, then administered a test battery consisting of the Depression 30, IPAT Anxiety Scale, Nowicki-Strickland Internal-External Scale, and Rosenberg Self-Esteem Scale. Following this, patients were matched into triads on the basis of pretest scores. Each member of the triad was then randomly assigned to one of three groups: insight-oriented, current events, control (nontreatment). At the end of 50 group sessions, all patients were reassessed using the same test battery. Results were analyzed by means of analysis of covariance and the nonparametric Friedman test. Post-hoc procedures were performed with the following results: 1) the insight-oriented therapy group was significantly less depressed than both the current events group and the control group and 2) both the therapy and the current events groups were significantly more internally oriented than the control. Not only does group therapy per se seem to benefit the MS patient, but any supervised group involvement appears to improve significantly patient emotional state.", "This study examined the efficacy of an 8-week telephone-administered cognitive-behavioral therapy (CBT) for the treatment of depressive symptomatology in multiple sclerosis (MS) patients. The treatment, Coping with MS (CMS), included a patient workbook designed to structure the treatment, provide visual aids, and help with homework assignments. Thirty-two patients with MS, who scored at least 15 on the Profile of Mood States Depression-Dejection scale, were randomly assigned to either the telephone CMS or to a usual-care control (UCC) condition. Depressive symptomatology decreased significantly in the CMS condition compared with the UCC condition. Furthermore, adherence to interferon beta-1a, a disease-modifying medication for the treatment of MS, was significantly better at the 4-month follow-up among patients who received CMS as compared with those in the UCC condition.", "This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG). and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments.", "Multiple sclerosis (MS) is a chronic, often progressive neurologic disorder characterized by cerebral and spinal cord lesions. Patients with advanced MS often require continuous supervision in a long-term skilled nursing facility. Many of these patients experience clinical levels of depression. For this experiment, we randomly assigned MS patients living in a skilled nursing facility to either a control condition or an extended treatment protocol. The protocol consisted of assigning individual certified nursing assistants (CNAs) to each patient, in-service training for the CNAs, and the use of memory notebooks. All patients completed the short version of the Beck Depression Inventory and several measures of cognitive functioning at the start and end of the study. The results indicate statistically and clinically significant improvements in the depression of patients in the treatment but not in the control condition. These results led to recommendations for the treatment of MS patients living in long-term skilled nursing facilities and for additional research.", "The chronic and progressive nature of multiple sclerosis (MS) often excludes patients from neuropsychological treatment. At the Multiple Sclerosis Rehabilitation Hospital, Haslev, 40 patients with mild to moderate cognitive and behavioral impairment associated with MS were randomized to either specific cognitive treatment (20 pts) by direct training, compensatory strategies and neuropsychotherapy, or to non-specific, deliberately diffuse mental stimulation (20 pts). Treatment was for a mean of 46 days. The effects of treatment were evaluated by neuropsychological tests before treatment, immediately after treatment (short-term effects) and 6 months later (long-term effects). After short-term treatment, effects on cognitive measures were not convincing, but on the Beck Depression Inventory (BDI) the specific cognitive treatment group reported significantly less depression. After 6 months only this group showed an effect, since the visuo-spatial memory was improved. However, the depression ratings (BDI) were almost maintained from the short-term level. Interestingly, the non-specific treatment group rated themselves as significantly more depressed. Conclusively, it is worth while to offer specific neuropsychological treatment to MS patients with cognitive and behavioral dysfunction.", "The researchers studied the effectiveness of a nursing intervention in promoting adjustment and symptom management in individuals with multiple sclerosis (MS). This was a 4-year longitudinal study to determine whether the 4-week intensive outpatient program was effective in increasing adjustment to MS and if the treatment effect would last over time. A sample of 27 individuals with MS participated in the study. Treatment participants had significant improvements in symptom management at the 4-year follow up. This improvement was attributable to signficant improvements in sleep and fatigue levels. Although adjustment and self-efficacy scores improved in the treatment group over time, this improvement was not superior to the control group. This was anticipated because the behavioral changes would precede improvement in adjustment to life following the diagnosis of MS." ]
"The diversity of psychological interventions identified indicates the many ways in which they can potentially help people with MS. No definite conclusions can be made from this review. However there is reasonable evidence that cognitive behavioural approaches are beneficial in the treatment of depression, and in helping people adjust to, and cope with, having MS."
"CD008039"
[ "11554954", "15482357", "16492236", "17563841", "15579612", "16618262", "8427430", "9825271" ]
[ "Efficacy of nonprescription doses of ibuprofen for treating migraine headache. a randomized controlled trial.", "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.", "Rofecoxib in the acute treatment of migraine: a randomized controlled clinical trial.", "Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.", "Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial.", "Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study.", "The efficacy of metoclopramide in the treatment of migraine headache.", "Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks." ]
[ "To evaluate the efficacy and safety of ibuprofen, 200 mg and 400 mg, compared with placebo and each other for the treatment of pain of migraine headache.\n Migraine headache is a common illness with significant social and economic impact.\n Randomized, placebo-controlled, double-blind trial of 6 hours' treatment duration.\n Fifteen investigators at 17 private practice and referral centers in the United States participated in this study of 660 outpatient adults aged 18 to 84 years with migraine headache of moderate to severe intensity. Each patient was randomly assigned to a single dose of study medication: ibuprofen 200 mg (n = 216) or 400 mg (n = 223), or placebo (n = 221). The percentage of patients with a reduction in baseline headache intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Secondary outcomes included other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none.\n Significantly (P < or = .006) more patients treated with ibuprofen, 200 mg or 400 mg, reported mild to no pain after 2 hours (41.7% and 40.8%, respectively), compared with those treated with placebo (28.1%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < or = .001) greater for patients treated with ibuprofen 200 mg or 400 mg (0.68 and 0.65, respectively), compared with those treated with placebo (0.39). Statistically significant differences in favor of both doses of ibuprofen over placebo were observed for mean pain intensity difference at 1 hour after treatment. In patients with severe baseline pain intensity, ibuprofen, 400 mg, was significantly (P < or = .048) superior to placebo for the primary efficacy end points, while ibuprofen, 200 mg, was not. Ibuprofen, 200 mg and 400 mg, were statistically significantly more effective than placebo for all clinically important secondary pain relief outcomes. Mean severity changes of migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < or = .03) in favor of both doses of ibuprofen over placebo, and results for the percentage of patients with symptoms reduced to none consistently, although less often statistically significant, favored ibuprofen. No statistically significant differences in adverse events were found among treatment groups.\n Ibuprofen at doses of 200 mg and 400 mg is an efficacious, cost-effective, well-tolerated, single-ingredient nonprescription treatment for pain of migraine headache. In addition, while not always statistically significant, ibuprofen provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.", "Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.", "To investigate the efficacy, tolerability, and safety of rofecoxib and ibuprofen for acute migraine treatment.\n Rofecoxib was effective and well tolerated in a previous study of treatment of a single migraine attack. We sought to replicate these findings for a single attack and also study the clinical profile of rofecoxib in the acute treatment of multiple migraine attacks. Ibuprofen was included as a reference nonselective NSAID.\n Adult migraineurs (n = 783) treated one migraine attack with either rofecoxib (25 or 50 mg), ibuprofen 400 mg, or placebo in a randomized, double-blind study. Patients could elect to enroll in a 3-month double-blind extension phase.\n In the single-attack phase, headache relief at 2 hours postdose was reported by 59.4%, 62.2%, and 57.7% of patients who took rofecoxib 25 mg, rofecoxib 50 mg, and ibuprofen 400 mg, respectively, versus 30.5% for placebo (all P < .001 vs placebo). The active drugs were statistically superior to placebo on a variety of additional measures. In the extension phase, the mean percentage of patients' attacks with headache relief at 2 hours postdose was 61.8% for rofecoxib 25 mg, 65.4% for rofecoxib 50 mg, and 59.3% for ibuprofen 400 mg. The mean percentage of patients' attacks with 24-hour sustained headache relief was greater for rofecoxib 50 mg (52.0%) than for rofecoxib 25 mg (47.8%, P < .050) or ibuprofen (39.0%, P < .010). In the single-attack phase, the adverse event rate was higher for rofecoxib 50 mg (37.8%) than placebo (27.8%, P < .050); rates were similar to placebo for rofecoxib 25 mg (32.0%, n.s.) and ibuprofen 400 mg (28.1%, n.s.). In the extension phase, treatment groups had similar adverse event rates.\n Rofecoxib 25 and 50 mg and ibuprofen 400 mg were effective and generally well tolerated in the acute treatment of migraine.", "The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.", "Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated.\n To study the efficacy of rofecoxib in migraine.\n In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2-6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0-3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted.\n One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16-62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks.\n Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack.", "Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine.\n Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief.\n There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036).\n AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.", "By evaluating the efficacy of metoclopramide alone and in combination with ibuprofen versus placebos, this study was designed to both evaluate the efficacy of metoclopramide and elucidate its mechanism of action in the treatment of migraine headache.\n The study was conducted over a two-year period and was a randomized, double-blind, placebo-controlled study.\n An urban teaching hospital.\n Patients enrolled were at least 18 years old and had recurring headaches with one or more of the following characteristics: unilateral, preceded by neurologic symptoms, significant nausea and vomiting, or mood changes and photophobia.\n Ten milligrams of metoclopramide or an equal volume of IV normal saline was given and 600 mg of ibuprofen or identical-appearing placebo was given orally at time 0. Patients rated their pain and nausea at time 0, 30 minutes, and 60 minutes using visual-analog scales.\n The differences in pain and nausea scores for the metoclopramide + placebos group versus the other three groups were tested using exact nonparametric (Mann-Whitney) statistical procedures. The metoclopramide + placebos group had significantly better relief of pain compared with the placebos + ibuprofen and placebos + placebos groups. The metoclopramide + placebos group had significantly better relief of nausea than the ibuprofen + placebos group; nausea scores for the placebos + placebos group could not be analyzed due to excessive variance from the other groups at baseline. The differences between the metoclopramide + placebos group and the metoclopramide + ibuprofen group were not statistically significant with regard to either pain or nausea.\n Metoclopramide is efficacious in the treatment of both the pain and nausea of migraine headache. This is a direct action that is not dependent on the concomitant administration of another agent.", "The purpose of this study was to evaluate the effectiveness of a new formulation of ibuprofen (ibuprofen-arginine [IA]) in the treatment of migraine attacks. This is a faster absorbed formulation as compared with ibuprofen alone. The rapidity of action is considered to be a crucial factor in the treatment of migraine attacks. Forty migraine patients participated in this multicenter, double-blind, crossover, randomized, placebo-controlled trial. Each patient was treated with a single oral dose of IA 400 mg or placebo during two consecutive migraine attacks. The results confirm the efficacy of IA, with a significant (p < 0.05) improvement in pain relief at 30 min after treatment. A statistically significant (p < 0.001) reduction in pain intensity was observed at 1, 2, 4 and 6 h after treatment with ibuprofen as compared with placebo. IA was well tolerated and our data indicate that this new formulation of ibuprofen is valuable in the treatment of acute migraine attacks." ]
"We found no new studies since the last version of this review. Ibuprofen is an effective treatment for acute migraine headaches, providing pain relief in about half of sufferers, but complete relief from pain and associated symptoms for only a minority. NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo, and soluble formulations provided more rapid relief. Adverse events were mostly mild and transient, occurring at the same rate as with placebo."
"CD003287"
[ "10526722", "11544612", "12757987", "10480767", "10321421", "12017407", "10834413", "11711322", "12873294", "11194244", "9686700", "10880892", "10480503", "10332684", "9183237", "9083709", "9000704", "11453959", "9167105", "12027927", "9444449", "15713351", "10332682", "12213353", "9250454", "15377436", "11476360", "11874927", "10784225", "12768948", "9032100", "9802741", "11553203", "12201618", "12873289", "9545126", "11694699", "12448933", "11131100", "11767232", "15523183", "11590992", "14557006", "14617222", "15111514", "9405901" ]
[ "Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.", "Severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia: a comparative study of insulin lispro and regular human insulin.", "Insulin lispro is as effective as regular insulin in optimising metabolic control and preserving beta-cell function at onset of type 1 diabetes mellitus.", "Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.", "Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.", "Comparison of insulin lispro with regular human insulin for the treatment of type 1 diabetes in adolescents.", "Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.", "A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump.", "Insulin lispro: a potential role in preventing nocturnal hypoglycaemia in young children with diabetes mellitus.", "Efficacy, safety, and pump compatibility of insulin aspart used in continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes.", "Use of the short-acting insulin analogue lispro in intensive treatment of type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection-meal.", "Improved blood glucose variability, HbA1c insuman Infusat and less insulin requirement in IDDM patients using insulin lispro in CSII. The Swedish Multicenter Lispro Insulin Study.", "Metabolic and immunologic effects of insulin lispro in gestational diabetes.", "Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.", "Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.", "Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group.", "Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.", "Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes.", "Health-related quality-of-life results from multinational clinical trials of insulin lispro. Assessing benefits of a new diabetes therapy.", "Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients.", "Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.", "The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes.", "Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.", "Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.", "Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human insulin analog in IDDM patients. A comparison with human regular insulin during a three-meal test period.", "Effect of insulin lispro on glycaemic control in Chinese diabetic patients receiving twice-daily regimens of insulin.", "Lispro insulin in type 1 diabetic patients on a Mediterranean or normal diet: a randomized, cross-over comparative study with regular insulin.", "Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes.", "A randomized, controlled trial comparing insulin lispro with human soluble insulin in patients with Type 1 diabetes on intensified insulin therapy. The UK Trial Group.", "Humalog Mix25 improves 24-hour plasma glucose profiles compared with the human insulin mixture 30/70 in patients with type 2 diabetes mellitus.", "Insulin lispro in CSII: results of a double-blind crossover study.", "Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group.", "Post-prandial insulin lispro vs. human regular insulin in prepubertal children with Type 1 diabetes mellitus.", "Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes.", "Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes.", "Human insulin analogue [LYS(B28), PRO(B29)]: the ideal pump insulin?", "Insulin lispro lowers postprandial glucose in prepubertal children with diabetes.", "Insulin lispro improves postprandial glucose control in patients with diabetes mellitus.", "Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial.", "A comparative study of insulin lispro and human regular insulin in patients with type 2 diabetes mellitus and secondary failure of oral hypoglycemic agents.", "Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study.", "Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.", "Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women.", "Comparison of additional metformin or NPH insulin to mealtime insulin lispro therapy with mealtime human insulin therapy in secondary OAD failure.", "A direct efficacy and safety comparison of insulin aspart, human soluble insulin, and human premix insulin (70/30) in patients with type 2 diabetes.", "Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. The Benelux-UK Insulin Lispro Study Group." ]
[ "To measure the effectiveness of insulin lispro, a fast-acting insulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy.\n In 11 diabetes outpatient clinics in the U.K., 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen. Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level.\n A total of 135 patients were randomized, with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction. Glycemic control was equally tight during treatment with human regular insulin (HbA1c, 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04). This difference was chiefly because of a reduced number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group.\n The use of a fast-acting insulin analog, insulin lispro, as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy.", "To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia. Research design and methods An open-label, randomised, 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness. The efficacy of each treatment was evaluated by glycaemic control (HbA(1c)), eight-point home blood glucose profiles, and the frequency and severity of hypoglycaemic episodes and quality of life.\n Eighteen (55%) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study. There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin (55 vs 84 episodes, p=0.087). This resulted principally from a 47% lower incidence of nocturnal severe hypoglycaemia with insulin lispro (25 vs 47 episodes, p=0.11). The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments (HbA(1c) 9.1% insulin lispro vs 9.3% regular human insulin).\n In individuals with type 1 diabetes, who have impaired awareness of hypoglycaemia, treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes. Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia, although a larger study is required to confirm these findings.\n Copyright 2001 John Wiley & Sons, Ltd.", "The aim of the study was to examine the effects of intensive insulin therapy using lispro on metabolic control, immunogenicity and beta-cell function of newly diagnosed type 1 diabetic subjects in comparison with intensive insulin therapy using regular insulin. An open study was conducted in 45 newly diagnosed type 1 diabetic subjects. Patients were randomly assigned to intensive insulin therapy using insulin lispro (lispro) (lispro, n=22; 22.8 years) or intensive insulin therapy using regular insulin (regular) (regular, n=23; 24.4 years): three to five injections of subcutaneous rapid-acting insulin before meals and Neutral Protamine Hagedorn (NPH) before dinner/bed-time. GAD, IA2, insulin antibodies, basal and stimulated plasma C-peptide and HbA(1c) were measured initially and at months 1, 4, 8 and 12. Daily blood glucose profiles tended to be lower in the lispro group, particularly values after breakfast, without reaching statistical significance. There were no differences in terms of HbA(1c) throughout the study. The proportion of subjects achieving an HbA(1c)<6% at the end of the study was similar in both groups (regular 73.9%, lispro 68.0%). The number of mild hypoglycemic episodes tended to be lower with lispro, but not significantly. beta-Cell function was not significantly different in both groups. During follow-up there were no differences in antibodies, including IAAb. In summary, insulin lispro used in intensive insulin therapy is as effective as regular insulin in optimizing metabolic control and preserving beta-cell function at diagnosis of type 1 diabetes.", "Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation (NPL) in a ratio of 25:75%. The objective of this study was to compare Humalog Mix25 to human insulin 30/70 (30% regular insulin/70% NPH) with respect to glycemic control.\n Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month randomized open-label two-period crossover study. Each insulin was administered twice daily, before the morning and evening meals. Information regarding self-monitored blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l), insulin dose, and HbA1c was collected.\n Treatment with Humalog Mix25 resulted in better postprandial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70. Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments.\n In comparison to treatment with human insulin 30/70, twice daily administration of Humalog Mix25 resulted in improved postprandial glycemic control, similar overall glycemic control, and the convenience of dosing immediately before meals.", "The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.", "Although insulin lispro (insulin LP) has been shown to improve postprandial blood glucose (BG) control and reduce hypoglycemic episodes in adult patients with type I diabetes, there appear to have been few clinical studies focusing on its use in adolescents.\n This study compared the effects of insulin LP with those of regular human insulin (insulin R) on postprandial BG control and hypoglycemia in adolescents with type diabetes.\n In this crossover, open-label study, adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were randomized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals, in addition to daily intermediate-acting insulin. After 4 months, patients were switched to the alternate treatment sequence. Eight-point BG profiles, hypoglycemia rate, and glycosylated hemoglobin (HbA1c) were measured at baseline and end point.\n Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries; 463 were randomized to treatment (228 insulin LP, 235 insulin R), and 457 completed the study. Insulin LP given before breakfast resulted in significantly lower mean (+/-SD) 2-hour postprandial BG levels compared with insulin R (9.7 +/- 4.0 mmol/L vs 10.6 +/- 4.3 mmol/L, respectively; P < 0.001). Insulin LP given before dinner resulted in significantly lower 2-hour postprandial BG levels compared with insulin R (8.6 +/- 3.5 mmol/L vs 9.3 +/- 3.7 mmol/L; P = 0.003). No differences were seen between treatments in 2-hour postprandial BG levels after the midday meal. Mean baseline HbA1c values were similar between sequence groups, and no between-group difference in HbA1c was observed at end point (insulin LP, 8.69% +/- 1.52%; insulin R, 8.70% +/- 1.65%). Treatment with insulin LP resulted in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R (4.02 +/- 4.5 vs 4.37 +/- 4.5, respectively; P = 0.023) and significantly fewer hypoglycemic episodes between midnight and 6 AM (1.0 +/- 1.9 vs 1.7 +/- 2.6; P < 0.001).\n In adolescents with type 1 diabetes, insulin LP significantly improved postprandial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population.", "To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI).\n This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals.\n Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups.\n Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.", "This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A(1c) (HbA(1c)) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA(1c) than was buffered regular human insulin (7.41+/-0.97 vs. 7.65+/-0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16+/-4.29 vs. 13.20+/-4.68 mmol/l; P=.012) and 2-h (9.64+/-4.10 vs. 12.53+/-4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.", "The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen.\n Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7-11 years) with T1DM on three injections/day; long-acting isophane insulin remained identical. At the end of each 4-month treatment arm, an overnight 15-min venous sampled blood glucose profile was performed.\n Despite similar blood glucose levels pre-evening meal (lispro vs. soluble: mean +/- se 6.5 +/- 1.0 vs. 7.1 +/- 1.1 mmol/l, P = 0.5), post-meal (18.00-22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 +/- 12 vs. 170 +/- 13 mmol min-1 l-1, P = 0.03). In contrast, in the early night (22.00-04.00 h) the prevalence of low blood glucose levels (< 3.5 mmol/l) was lower on lispro (8% of blood glucose levels) than on soluble insulin (13%, P = 0.01). In the early morning (04.00-07.00 h) mean blood glucose and prevalence of low levels were no different between the two treatment groups, and fasting (07.00 h) blood glucose levels were similar (6.1 +/- 0.8 vs. 6.3 +/- 0.9 mmol/l, P = 0.8). At the end of each treatment arm there were no differences in HbA1c (lispro vs. soluble 8.6% vs. 8.4%, P = 0.3), or in insulin doses (mean, range 0.97, 0.68-1.26 vs. 0.96, 0.53-1.22 U/kg per day, P = 0.2).\n The shorter duration of action of insulin lispro given before the evening meal may reduce the prevalence of early nocturnal hypoglycaemia without compromising HbA1c in young children with T1DM.", "The purpose of this study was to compare the efficacy, safety and pump compatibility of insulin aspart (a rapid-acting insulin analog) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion (CSII) therapy.\n This was a single-center randomized open-label study Patients received CSII therapy with insulin aspart (n = 19) or buffered regular human insulin (n = 10) for 7 weeks. Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals.\n Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels (8.2 +/- 1.9 and 8.5 +/- 2.1 mmol/l, respectively) (mean +/- SD) and maintaining serum fructosamine (343 +/- 25.7 and 336 +/- 27.4 micromol/l) and HbA1c (6.9 +/- 0.6 and 7.1 +/- 0.6%) levels. Possible obstructions and set leakages were infrequently reported in both groups. Similar numbers of patients experienced hypoglycemia (blood glucose <2.5 mmol/l): 14 (74%) insulin aspart patients versus 6 (60%) buffered regular human insulin patients. Patients receiving insulin aspart had fewer hypoglycemic events per patient (2.9) than those patients receiving buffered regular human insulin (6.2). There were no differences between the two insulins in the occurrence of hyperglycemic events (blood glucose >19 mmol/l) or in the number and type of adverse events.\n Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy.", "To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conventional insulins, 69 patients on intensive therapy (4 daily s.c. insulin injections, soluble at each meal, NPH at bedtime, HbA1c <7.5%) were studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions (Groups I-IV). Lispro was always injected at mealtime, soluble 10-40 min prior to meals (with the exception of Group IV). Bedtime NPH was continued with both treatments. When lispro replaced soluble with no increase in number of daily NPH injections (Group I, n = 15), HbA1c was no different (p = NS), but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3-4 times daily, lispro (Group II, n = 18), but not soluble (Group III, n = 12) decreased HbA1c by 0.35 +/- 0.25% with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA1c increased by 0.18 +/- 0.15% and hypoglycaemia was more frequent than when soluble was injected 10-40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin.", "The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in continuous subcutaneous insulin infusion (CSII) therapy with respect to blood glucose control as expressed by the standard deviation of blood glucose (SD(BG) ) and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ) parameters during such treatment. Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label, randomized, cross-over, multicenter study for 4 months (2 months LP and 2 months I or vice versa). Boluses with LP were given 5 min before each meal and with I 30 min before each meal. During LP administration compared with I, the SD(BG) of all blood glucose values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were significantly reduced. The HbA(1c) was significantly lower during LP administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per 30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total amount of daily insulin was slightly but significantly lower with LP, compared to I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control, a lower HbA(1c), a less insulin requirement without increasing the frequency of hypoglycemia.", "To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective.\n We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer.\n Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group.\n Insulin lispro may be considered a treatment option for women with gestational diabetes.", "To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose.\n A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied.\n The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05), but not in group 3 (NS) vs. group 1.", "Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy. It has a fast absorption rate and short duration of action. The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been tested.\n To compare insulin lispro and human regular insulin in the mealtime treatment of patients with NIDDM.\n A 6-month, randomized, multinational (16 countries), multicenter (80 sites) clinical trial with an open-label, crossover design was performed in 722 patients with NIDDM. Insulin lispro was injected immediately before and human regular insulin 30 to 45 minutes before the meal.\n Throughout the study, the postprandial rise in serum glucose levels was significantly lower during insulin lispro than human regular insulin treatment. At end point the rise (mean +/- SEM) in serum glucose levels was 30% lower at 1 hour (2.6 +/- 0.1 mmol/L [46.8 +/- 1.8 mg/ dL] for lispro vs 3.7 +/- 0.1 mmol/L [66.6 +/- 1.8 mg/dL] for human regular insulin) and 53% lower 2 hours after the test meal (1.4 +/- 0.1 mmol/L [25.2 +/- 1.8 mg/dL] for lispro vs 3.0 +/- 0.1 mmol/L [54.0 +/- 1.8 mg/dL] for human regular insulin) with insulin lispro compared with human regular insulin therapy (P < .001 for both intervals). During insulin lispro therapy the rate of hypoglycemia overall (P = .01) and overnight (P < .001) was lower and the number of asymptomatic hypoglycemic episodes was smaller (P = .03) than during human regular insulin therapy. Associated with a similar 13% increase (P < .001) in the total daily insulin dose, the glycosylated hemoglobin level decreased (P < .001) equally in both treatment groups. Serum lipid and lipoprotein levels remained unchanged. There were no differences in the adverse events between the 2 treatment groups.\n Compared with human regular insulin therapy, mealtime therapy with insulin lispro reduced postprandial hyperglycemia and may decrease the rate of mild hypoglycemic episodes in patients with NIDDM.", "The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus (IDDM) and 295 patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were randomized to inject either regular human insulin 30 to 45 minutes before eating, or insulin lispro immediately before each meal, in addition to basal insulin. The postprandial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy. At end point the increment was significantly lower at 1 hour (35%) and at 2 hours (64%) after the meal in IDDM patients; in NIDDM patients, the increment was nonsignificantly lower at 1 hour (19%) and significantly lower at 2 hours (48%). IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin (HbA1c) levels in patients receiving regular human insulin (8.1% vs 8.3%). In NIDDM patients, HbA1c levels decreased equally in both treatment groups. Due to its fast absorption rate, insulin lispro improves postprandial control in diabetes. Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience.", "Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.", "IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).\n Twelve patients with type 1 diabetes, age 47.8 +/- 2.4 years (mean +/- SEM), body mass index 26.5 +/- 1.0 kg/m2, diabetes duration 30.5 +/- 3.2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.\n Lispro gave a marked insulin peak of 135 +/- 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0.01). Plasma IGF-I concentration was 78.8 +/- 10.9 microg/l on lispro and 82.3 +/- 10.5 microg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0.006) but glycosylated haemoglobin (HbA1c) was 6.4 +/- 0.2% on both therapies.\n Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.", "To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R).\n We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses.\n Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies.\n Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility.", "To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes.\n People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level.\n BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments.\n Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.", "A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher post-prandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-prandial glycemic control without increasing the risk of hypoglycemia.", "A variety of abnormalities of metabolic, haemostatic and endothelial markers are associated with Type 2 diabetes. Evidence suggests that poor post-prandial blood glucose control may contribute to vascular risk. We aimed to examine whether the restoration of a more physiological insulin profile post-prandially would improve these abnormalities. Twenty-one patients with insulin-treated Type 2 diabetes were recruited into a single centre, crossover, double-blind study. Patients were randomized to unmodified human insulin or insulin aspart before main meals for 6-week study periods, both together with NPH insulin. At the end of each study period, pre-breakfast levels of markers of vascular risk were assessed and a test meal performed. There was no significant difference in HbA(1c) (7.04 +/- 0.13% (+/-S.E.) versus 7.15 +/- 0.11%, P = 0.060) with insulin aspart compared to human insulin at the end of each study period. The mean post-prandial blood glucose concentration at 90 min from self-monitored results was lower with insulin aspart than with human insulin (7.9 +/- 0.4 mmol/l versus 9.3 +/- 0.4 mmol/l, P = 0.011) as was study day post-prandial blood glucose at 90 min (8.4 +/- 0.5 mmol/l versus 9.2 +/- 0.6 mmol/l, P = 0.046). No significant differences were found in fasting lipid profile, apolipoproteins, fibrinogen, plasminogen activator inhibitor-1, E-selectin, or homocysteine between the two study periods. Insulin aspart resulted in improved post-prandial glycaemic control when compared to human insulin in Type 2 diabetic patients, but this was not associated with changes in markers of vascular risk.", "Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps.\n A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire.\n The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro.\n Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.", "To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes.\n Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34.\n 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17).\n Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c) values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA(1c) values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy.\n The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.", "The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/- SD]).\n After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day.\n During the treatment periods, glycemic control was stable during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48, NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels.\n Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h.", "nan", "Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.", "To compare the safety and efficacy of insulin aspart (IAsp), buffered regular insulin (BR), and insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes.\n After completing a 4-week run-in period with BR, 146 adult patients with type 1 diabetes (with pretrial CSII experience) were randomly assigned (2:2:1) to CSII treatment with IAsp, BR, or lispro for 16 weeks in a multicenter, open-label, randomized, parallel-group study. Bolus insulin doses were administered 30 min before meals (BR) or immediately before meals (IAsp or lispro).\n Treatment groups had similar baseline HbA(1c) (7.3% +/- 0.7 for IAsp, 7.5% +/- 0.8 for BR, and 7.3% +/- 0.7 for lispro). After 16 weeks of treatment, HbA1c values were relatively unchanged from baseline, and the mean changes in baseline HbA1c values were not significantly different between the three groups (0.00 +/- 0.51, 0.15 +/- 0.63, and 0.18 +/- 0.84 for the IAsp, BR, and lispro groups, respectively). The rates of hypoglycemic episodes (blood glucose <50 mg/dl) per patient per month were similar (3.7, 4.8, and 4.4 for the IAsp, BR, and lispro groups, respectively). Clogs/blockages in pumps or infusion sets were infrequent; most subjects (76, 83, and 75% in the IAsp, BR, and lispro groups, respectively) had < or = 1 clog or blockage per 4 weeks during the trial.\n Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps.", "Despite considerable experience with insulin lispro, few blinded comparisons with soluble insulin are available. This study compared insulin lispro with human soluble insulin in patients with Type 1 diabetes mellitus on multiple injection therapy who inject shortly before meals.\n Glucose control, frequency of hypoglycaemia and patient preference were examined in the course of a prospective, randomized, double-blind, crossover comparison, with a 6-week run-in period and 12 weeks on each therapy. Ninety-three patients took part, all on multiple daily doses of insulin, with soluble insulin before meals and NPH (isophane) insulin at night. The main outcome measures were self-monitored blood glucose profiles, glycated haemoglobin, frequency of hypoglycaemic episodes, patient satisfaction and well-being and patient preference.\n Blood glucose levels were significantly lower after breakfast and lunch, but higher before breakfast, lunch and supper, in patients taking insulin lispro. Levels of HbA(1c) were 7.4 +/- 1.1% on Humulin S and 7.5 +/- 1.1% on insulin lispro (P = 0.807). The overall frequency of symptomatic hypoglycaemia did not differ, but patients on insulin lispro were less likely to experience hypoglycaemia between midnight and 6 a.m., and more likely to experience episodes from 6 a.m. to midday. Questionnaires completed by 84/87 patients at the end of the study showed that 43 (51%) were able to identify each insulin correctly, nine (11%) were incorrect, and 32 (38%) were unable to tell the insulins apart. No significant preference emerged: 35 (42%) opted for insulin lispro, 24 (29%) opted for Humulin S, while the remainder had no clear preference.\n Substitution of insulin lispro for soluble insulin in a multiple injection regimen improved post-prandial glucose control at the expense of an increase in fasting and pre-prandial glucose levels. Patients who already injected shortly before meals expressed no clear preference for the fast-acting analogue, and did not improve their overall control as a result of using it. Nocturnal hypoglycaemia was however, less frequent on insulin lispro, and may emerge as a robust indication for its use.", "To compare the effects of Humalog Mix25 (Humalog Mix75/25 in the USA) (Mix25) and human insulin 30/70 (30/70) on the 24-hour inpatient plasma glucose (PG) profile in patients with type 2 diabetes mellitus (T2DM).\n A randomised, open-label, 8-week crossover study. Study insulins were injected twice daily, 5 minutes before breakfast and dinner.\n Four-week outpatient (dose-adjustment) treatment phase, and 3-day inpatient (test) phase.\n Twenty-five insulin-treated patients with T2DM (ages 40-66 years), mean (+/- standard error of the mean) (SEM) HbA1c 7.7% +/- 0.23%, and body mass index (BMI) 29.3 +/- 0.83 kg/m2.\n 24-hour PG profiles, PG excursions after meals, PG area under the curve (AUC), and 30-day hypoglycaemia rate.\n The 2-hour PG excursions following breakfast (5.5 +/- 0.34 v. 7.2 +/- 0.34 mmol/l, p = 0.002) and dinner (2.4 +/- 0.27 v. 3.4 +/- 0.27 mmol/l, p = 0.018) were smaller with Mix25 than with 30/70. PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 (77.6 +/- 3.8 v. 89.5 +/- 4.3 mmol/h/ml, p = 0.001). PG AUC between lunch and dinner, dinner and bedtime, and bedtime and breakfast did not differ between treatments. Pre-meal and nocturnal PG were comparable. The postprandial insulin requirement for lunch meals was supplied equally by the two insulin treatments. The thirty-day hypoglycaemia rate was low (Mix25 0.049 +/- 0.018 v. 30/70 0.100 +/- 0.018 episodes/patient/30 days, p = 0.586) for both treatments.\n In patients with T2DM, Mix25 improved the 24-hour PG profile with lower postprandial PG excursions than with human insulin 30/70.", "Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection, resulting in higher insulin levels at an earlier point in time and a shorter duration of action. The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postprandial and overall control in 30 IDDM patients (age, 35.1 +/- 1.5 years; male-female ratio, 17:13; BMI, 24.8 +/- 0.5 kg/m2; HbA1c, 8.03 +/- 0.13% at baseline) treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) in a double-blind crossover clinical study. Patients were randomized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months. All meal boluses were given immediately before breakfast, lunch, and supper. An eight-point blood glucose profile was measured once weekly, and HbA1c levels were measured monthly. At the end of the 3-month treatment period, HbA1c levels were significantly lower with insulin lispro, compared with human regular insulin: 7.66 +/- 0.13 vs. 8.00 +/- 0.16% (P = 0.0041). While preprandial, bedtime, and 2:00 A.M. values for blood glucose were not significantly different, 1-h postprandial blood glucose was significantly improved after breakfast, lunch, and dinner with insulin lispro, compared with human regular insulin: 8.35 vs. 9.79 mmol/l (P = 0.006), 7.58 vs. 8.74 mmol/l (P = 0.049), and 7.85 vs. 9.01 mmol/l (P = 0.03). The incidence of hypoglycemia per 30 days (blood glucose levels, <3.0 mmol/l) was 8.4 +/- 1.3 before randomization, decreasing to 6.0 +/- 0.9 for insulin lispro and to 7.6 +/- 1.3 for regular insulin during the last month of the study. Two patients in each group reported insulin precipitation. We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia.", "To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment.\n This was a multicenter randomized double-blind crossover study of 90 male subjects with type 1 diabetes. Insulin aspart or soluble human insulin was administered before meals, and NPH insulin was administered at bedtime as basal therapy. Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile.\n The 24-h plasma glucose control obtained with insulin aspart, as assessed by excursions of blood glucose outside a predefined normal range (4.0-7.0 mmo/l), was superior (22% reduction in excursion, P < 0.01). Fructosamine levels remained unchanged with insulin aspart, with daytime glycemic control superior but nighttime glycemic control inferior. Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postprandial blood glucose control after lunch and dinner (P < 0.05) without deterioration of preprandial blood glucose control. Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin (20 vs. 44 events, P < 0.002). Insulin aspart was well tolerated.\n In comparison with human insulin, insulin aspart can improve postprandial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes. For its full potential to be realized, it will need to provide better control of nighttime hyperglycemia.", "To study whether post-prandial insulin lispro (PL) could be used as a part of insulin therapy instead of premeal human regular insulin (HR) in prepubertal children with Type 1 diabetes mellitus (Type 1 DM).\n In this open, randomized cross-over study patients used either PL or HR at breakfast and at dinner. After a 1-month screening period, patients were randomized to treatment with PL or HR for 3 months and then they crossed over to the other insulin for an additional 3 months. The patients were 24 prepubertal children with Type 1 DM (median age 6.2 years, duration of diabetes 37 months). Home monitoring of 1-day glucose profiles at meals (premeal, 1 h and 2 h after breakfast and after dinner) and HbA1c were measured before randomization, before cross-over, and at the last visit. Data on hypoglycaemic episodes were collected at each of the seven visits. The variables were compared between the two treatments.\n Of the patients 22/24 completed the study. There were no major differences in the glucose excursions between PL and HR after breakfast (mean +/- SD: 1-h PL 3.7 +/- 4.7 vs. HR 2.9 +/- 3.9 mmol/l, P = 0.3; 2-h -0.9 +/- 5.4 vs. 0.3 +/- 4.5 mmol/l, P = 0.2, respectively) or after dinner (1-h PL -2.5 +/- 4.8 vs. HR -0.4 +/- 3.7 mmol/l, P = 0.07, 2-h -4.1 +/- 5.2 vs. -0.7 +/- 5.0 mmol/l, P = 0.05, respectively). Mean change of HbA1c was similar in both treatment groups (PL 0.2 +/- 0.8% vs. HR -0.4 +/- 0.7%, P = 0.1). The frequency of hypoglycaemic episodes was 4.9 per patient per month during treatment with PL, and 4.4 during HR (P = 0.3).\n Treatment with post-prandial lispro as a meal insulin is as effective and safe as traditional treatment with regular insulin in young children.", "To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes.\n Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5 min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a 339 kcal breakfast.\n The 2-h postprandial PG was significantly lower with Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p = 0.001). The maximum decrease in PG over 6 h, after exercise onset, was significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p < 0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3 episodes/30 d; p = 0.042).\n Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.", "To compare quality of life (QoL) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue, insulin aspart (IAsp), with that in patients receiving soluble human insulin (HI).\n In this 6-month, multinational, randomized, open-label trial, 424 patients from German-speaking countries were subjected to psychometric assessment before and after randomization (ratio 2 : 1) to basal-bolus treatment with either IAsp (n = 283) or HI (n = 141). Patients on HI were advised to keep an injection-meal interval of 30 min, whereas patients on IAsp were advised to inject immediately before meals. Treatment satisfaction and diabetes-related QoL were assessed using validated instruments to measure the domains of patients' individual treatment goals, physical complaints, worries about the future, social relations, leisure time flexibility, daily hassles, diet restrictions, burdens and fear of hypoglycaemia, blood glucose fluctuations, self-efficacy, and fear of insulin analogues.\n After 6 months, IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales (P < 0.01), and in QoL with respect to diet restrictions (P < 0.01). Improved satisfaction was mainly due to increased dietary and leisure time flexibility (P < 0.0001). Twenty-three percent of the IAsp group vs. 14% of the HI group achieved small but important improvements of total QoL (between-group difference, P < 0.06). The number needed to treat (NNT) with IAsp for an important increase in QoL was calculated to be 10. Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength (P < 0.01; NNT = 7) and patients feeling less protected against hypoglycaemia (P < 0.005; NNT = 8) as being the most likely to benefit from IAsp.\n Under these study conditions, IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin. The 'numbers needed to treat' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial.", "The short-acting insulin analogue lispro ([LYS(B28), PRO(B29)] is absorbed from the subcutis more rapidly than soluble insulin (S). To compare the clinical effectiveness of lispro vs S, 11 Type 1 patients using continuous subcutaneous insulin infusion (CSII) therapy (6 F, 5 M, age 30 +/- 2.5 years, diabetes duration 14 +/- 1.0 years, BMI 24.0 +/- 0.8 kg m(-2), HbA1c 6.5 +/- 0.2%) were studied in an open, randomized, crossover study for 6 months (3 months lispro and 3 months S or vice versa). During lispro treatment mean fasting and 2 h postprandial blood glucose were lower compared to the S phase (fasting 6.5 +/- 0.4 vs 7.5 +/- 0.4 mmol l(-1) (NS), postprandial 6.8 +/- 0.3 vs 8.3 +/- 0.3 mmol l(-1), p = 0.03). In patients treated first with lispro HbA1c levels improved from 6.3 +/- 0.2% to 5.7 +/- 0.3%; On reversion to S HbA1c increased to 6.2 +/- 0.2%. In the group treated first with S, HbA1c fell (6.7 +/- 0.4% vs 6.5 +/- 0.3%) and then improved further to 6.3 +/- 0.3% with lispro. None of these changes were significant. There was no significant difference with respect to hypoglycaemic or other adverse events. It can be concluded that lispro in CSII therapy is safe and may improve postprandial glucose excursions.", "This study compared the glucose-lowering effect of insulin lispro, given before or after meals, with regular human insulin given before meals in prepubertal children with diabetes.\n A 3-way crossover, open-label study involving 61 prepubertal children (ages 2.9-11.4 years) with type 1 diabetes. The children were randomly assigned to receive regular human insulin 30 to 45 minutes before meals, insulin lispro within 15 minutes before or immediately after meals, combined with basal insulin. Each treatment lasted 3 months. Hemoglobin A(1c) levels and home glucose monitoring profiles were measured at the end of each treatment period.\n Treatment with insulin lispro before breakfast resulted in lower 2-hour postprandial glucose values than regular human insulin (11.7 +/- 4.4 mmol/L vs 15.0 +/- 5.4 mmol/L). Similarly, insulin lispro given before dinner resulted in lower blood glucose values 2 hours postprandially (8.8 +/- 5.0 mmol/L vs 10.8 +/- 5.4 mmol/L) than regular human insulin. When insulin lispro was administered after meals, the 2-hour glucose levels were between those seen with either insulin lispro or regular human insulin given before meals. The number and types of adverse events, the rates of hypoglycemia, and the HbA(1c) levels did not differ among the 3 therapies.\n In prepubertal children, insulin lispro given before meals is safe and significantly lowers postprandial glucose levels after breakfast and dinner compared with regular human insulin, and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal.", "Insulin lispro was compared with regular human insulin with respect to glycaemic control in patients with diabetes mellitus on intensive insulin treatment. Sixty-two patients (55 type 1; 7 type 2) from eight study centres in the Czech Republic, Slovenia and the Slovak Republic participated in a 4-month, open-label, randomized, crossover study. Patients administered insulin lispro immediately before meals or regular human insulin 30 min before meals. A test meal (220-400 kcal), based on local and individual dietary habits and consistent for each patient throughout the study was given at baseline and at the end of each treatment. At each test meal visit HbA1c, fasting blood glucose, 1-hour and 2-hour postprandial blood glucose levels were measured. The level of HbA1c (7.6% +/- 1.5% versus 7.4% +/- 1.5%), incidence of hypoglycaemia (41-66% of patients--versus 39-63%) and daily insulin dose (0.67 +/- 0.11 U/kg versus 0.65 +/- 0.11 U/kg) did not differ between treatment groups at endpoint (insulin lispro versus regular human insulin, respectively). Mean 2-hour postprandial blood glucose excursion for the insulin lispro group (0.0 +/- 3.7 mmol/L) was significantly lower (p = 0.035) when compared with the regular human insulin group (1.3 +/- 3.7 mmol/L) at endpoint. Therapy with insulin lispro was therefore associated with a significant improvement in postprandial blood glucose excursion control when compared with regular human insulin, without an increase in rate of hypoglycaemia.", "To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus.\n Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events.\n After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03-0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted -0.6 to -1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7-0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2-3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59-1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4-6 h) events (1.8 vs. 5.0% of patients, P < 0.005).\n These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus.", "To compare the effects of insulin lispro (LP) and human regular insulin (HR) when given twice daily with NPH insulin on glycemic control (HbA1c), daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs.\n A 5.5-month randomized, open-label, parallel study of 148 patients receiving either LP (n = 70) or HR (n = 78). Eight-point blood glucose profiles and HbA1c measurements were collected at baseline, 1.5, 3.5 and 5.5 months.\n Two-hour post-breakfast and 2-hour post-supper blood glucose levels (means [and standard errors]) were significantly lower for LP than for HR at the end point (9.5 [0.4] mmol/L v. 10.9 [0.4] mmol/L and 8.4 [0.4] mmol/L v. 9.7 [0.4] mmol/L, respectively, p = 0.02 in both cases). HbA1c improved from 10.5% (0.2%) (LP) and 10.3% (0.2%) (HR) to 8.0% (0.1%). Hypoglycemia rates were similar during the day; however, there was an overnight trend to reduced rates with LP (0.08 [0.03] episodes/30 d v. 0.16 [0.04] episodes/30 d, p = 0.057). Quality-of life assessment showed significant improvement (p < 0.05) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened.\n With traditional twice-daily insulin administration algorithms, LP improves 2-hour postprandial glucose levels, quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control (HbA1c) compared with HR to insulin-naïve patients with type 2 diabetes who require insulin.", "To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII).\n 27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH.\n Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01).\n LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.", "While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients.\n Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001).\n Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.", "To compare maternal glucose levels and neonatal outcome, achieved in women with gestational diabetes (GDM) receiving either regular insulin or insulin lispro, with those of a control group of non-diabetic pregnant women.\n We enrolled 49 pregnant women with GDM, randomly allocated to the treatment with either insulin lispro (n=25) or regular insulin (n=24), and 50 pregnant women with normal GCT, matched for age, parity, pre-pregnancy weight and BMI, who formed the control group. All the women were caucasian, non-obese, with a singleton pregnancy and delivered term live born infants. Women of both groups were requested to perform a blood glucose profile (consisting of nine determinations: fasting/pre-prandial, 1 and 2h post-prandial) every week from the time of diagnosis to 38 weeks (study subgroups) or every 2 weeks from 28 to 38 weeks' gestation (control group).\n Overall pre-prandial blood glucose values in diabetic women were significantly higher than those of controls; at the 1h post-prandial time point, blood glucose values of GDM women receiving insulin lispro were similar to those of controls, whereas in the regular group they were significantly higher. Overall, both the lispro and regular insulin obtained optimal metabolic control at the 2h post-prandial time point, although near-normal blood glucose levels 2h after lunch could be observed only in the lispro group. There were no statistically significant differences between the groups in neonatal outcome and anthropometric characteristics; however, the rate of infants with a cranial-thoracic circumference (CC/CT) ratio between the 10th and the 25th percentile was significantly higher in the group treated with regular insulin in comparison to the lispro and control groups.\n Fasting/pre-prandial and 1h post-prandial maternal blood glucose levels in non-diabetic pregnant women fell well below the currently accepted criteria of glycemic normality in diabetic pregnancies. In women with GDM, the use of insulin lispro enabled the attainment of near-normal glucose levels at the 1h post-prandial time point and was associated with normal anthropometric characteristics; the use of regular insulin was not able to blunt the 1h peak post-prandial response to a near-normal extent and resulted in infants with a tendency toward the disproportionate growth. Insulin lispro can be regarded as a valuable option for the treatment of gestational diabetes.", "It has been found that non-fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels. In this study, we aimed to assess the effects of three different insulin regimens (group I: lispro insulin + NPH insulin, group II: lispro insulin + metformin and group III: regular insulin + NPH insulin) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti-diabetic drug failure.\n Sixty type 2 diabetic patients with secondary OAD failure were randomly allocated into three different treatment groups equally. There were no significant differences between groups concerning age, body mass index, diabetes duration, HbA1c and serum lipid levels at the beginning of the study. During the 6-month treatment period, blood glucose levels were determined 10 times during 24 h at pre-meal, post-prandial 1 and 2 h and at bedtime.\n Group I was found to be the most effective treatment regimen in controlling HbA1c levels (group I vs. group II, p = 0.013; group I vs. group III, p = 0.001; group II vs. group III, p > 0.05). When the comparison was made in each group, change in HbA1c was statistically significant for all groups (-3.18%, p = 0.001; -2.02%, p = 0.043 and -2.66%, p = 0.008 respectively). Group I was found to be more effective in controlling fasting and post-prandial plasma glucose levels measured at all times during the day when compared with group II and group III. In group II triglyceride levels were found to be significantly reduced, whereas other groups had no effect on lipids. No serious hypoglycaemic episodes were observed in any of the cases, whereas in group I hypoglycaemic episode rates were increased (chi2 = 8.843, p = 0.012).\n Lispro insulin plus NPH insulin regimen is more effective in controlling both pre- and post-prandial glucose levels and HbA1c when compared to regular insulin plus NPH insulin combination. Mealtime lispro insulin plus metformin combination therapy should also be seriously considered as an effective and alternative treatment regimen. It is worthy of attention that insulin lispro plus metformin lowered triglyceride levels.", "Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX).\n A total of 231 type 2 diabetic patients were randomized to insulin aspart (n = 75), HI (n = 80), or MIX (n = 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA1c, 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was \"change of HbA1c\" from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests.\n HbA1c decreased 0.91 +/- 1.00 for insulin aspart, 0.73 +/- 0.87 for HI, and 0.65 +/- 1.10 for MIX with the following confidence intervals: insulin aspart HI (-0.21 to 0.57, P = 0.025), insulin aspart MIX (-0.17 to 0.69, P = 0.092), and HI-MIX (-0.33 to 0.48, P = 0.006). Postprandial blood glucose decreased in the insulin aspart group: 0.44 mmol/l to >1.67 mmol/l compared with HI and 1.1 mmol/l to >1.67 mmol/l compared with MIX. Preprandial insulin doses were similar in the insulin aspart and HI groups (10-14.5 U). Hypoglycemic events per month were 0.56 HI, 0.40 insulin aspart, and 0.19 MIX.\n Statistically, insulin aspart was not equivalent to another treatment in terms of HbA1c reduction. Insulin aspart treatment resulted in improved HbA1c and postprandial blood glucose. The application of insulin aspart was safe and well tolerated.", "Several studies have suggested that use of the short-acting insulin analog, insulin lispro, in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin. This effect might be more pronounced in well-controlled patients, since intensive treatment of IDDM increases the rate of severe hypoglycemic events. This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients.\n This was an open, randomized, 6-month crossover study of 199 IDDM patients. Glycemic control was evaluated by HbA1c, home blood glucose measurements, and rate and timing of hypoglycemic events. At the end of the study, patients completed an evaluation form regarding therapy-related quality of life.\n HbA1c remained constant at approximately 7.3% throughout the study. Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin (mean -0.8 +/- 1.7 vs. 1.1 +/- 1.6 mmol/l, P < 0.001), as was the within-day variability (M value 27.7 +/- 19.7 vs. 30.2 +/- 23.1, P = 0.007). The incidence of severe hypoglycemic events (58 vs. 36, P = 0.037) including coma (16 vs. 3, P = 0.004) was significantly lower with insulin lispro than with regular insulin. Patients felt that insulin lispro increased flexibility and freedom of lifestyle.\n In well-controlled IDDM patients, insulin lispro is associated with a lower risk of severe hypoglycemia and coma." ]
"Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child."
"CD008194"
[ "16322168", "15671460" ]
[ "A randomized, controlled trial of the effectiveness of community-based case management in insuring uninsured Latino children.", "The State Children's Health Insurance Program: a multicenter trial of outreach through the emergency department." ]
[ "Lack of health insurance adversely affects children's health. Eight million US children are uninsured, with Latinos being the racial/ethnic group at greatest risk for being uninsured. A randomized, controlled trial comparing the effectiveness of various public insurance strategies for insuring uninsured children has never been conducted.\n To evaluate whether case managers are more effective than traditional methods in insuring uninsured Latino children.\n Randomized, controlled trial conducted from May 2002 to August 2004.\n A total of 275 uninsured Latino children and their parents were recruited from urban community sites in Boston.\n Uninsured children were assigned randomly to an intervention group with trained case managers or a control group that received traditional Medicaid and State Children's Health Insurance Program (SCHIP) outreach and enrollment. Case managers provided information on program eligibility, helped families complete insurance applications, acted as a family liaison with Medicaid/SCHIP, and assisted in maintaining coverage.\n Obtaining health insurance, coverage continuity, the time to obtain coverage, and parental satisfaction with the process of obtaining insurance for children were assessed. Subjects were contacted monthly for 1 year to monitor outcomes by a researcher blinded with respect to group assignment.\n One hundred thirty-nine subjects were assigned randomly to the intervention group and 136 to the control group. Intervention group children were significantly more likely to obtain health insurance (96% vs 57%) and had approximately 8 times the adjusted odds (odds ratio: 7.78; 95% confidence interval: 5.20-11.64) of obtaining insurance. Seventy-eight percent of intervention group children were insured continuously, compared with 30% of control group children. Intervention group children obtained insurance significantly faster (mean: 87.5 vs 134.8 days), and their parents were significantly more satisfied with the process of obtaining insurance.\n Community-based case managers are more effective than traditional Medicaid/SCHIP outreach and enrollment in insuring uninsured Latino children. Case management may be a useful mechanism to reduce the number of uninsured children, especially among high-risk populations.", "We evaluated emergency department (ED)-based outreach for the State Children's Health Insurance Program (SCHIP).\n We conducted a multicenter trial among uninsured children (< or = 18 years) who presented to 5 EDs in 2001 and 2002. On-site staff enrolled consecutive subjects for a control period followed by an intervention period during which staff handed out SCHIP applications to the uninsured. The primary outcome was state-level confirmation of insured status at 90 days.\n We followed 223 subjects (108 control, 115 intervention) by both phone interview and state records. Compared to control subjects, those receiving a SCHIP application were more likely to have state health insurance at 90 days (42% vs 28%; P<.05; odds ratio [OR]=3.8; 95% confidence interval [CI]=1.7, 8.6). Although the intervention effect was prominent among 118 African Americans (50% insured after intervention vs 31% of controls, P<.05), lack of family enrollment in other public assistance programs was the primary predictor of intervention success (OR=3.7; 95% CI=1.6, 8.4).\n Handing out insurance applications in the ED can be an effective SCHIP enrollment strategy, particularly among minority children without connections to the social welfare system. Adopted nationwide, this simple strategy could initiate insurance coverage for more than a quarter million additional children each year." ]
"The two studies included in this review provide evidence that in the US providing health insurance information and application assistance, and handing out application materials in hospital emergency departments can probably both improve insurance coverage of children. Further studies evaluating the effectiveness of different outreach strategies for expanding health insurance coverage of children in different countries are needed, with careful attention given to study design."
"CD000505"
[ "671204", "683224", "8477163", "463541", "7666265" ]
[ "Umbilical artery catheters: high, low, or no.", "Low positioning of umbilical-artery catheters increases associated complications in newborn infants.", "Randomized trial of umbilical arterial catheter position: clinical outcome.", "Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position.", "The association of heparin exposure with intraventricular hemorrhage among very low birth weight infants." ]
[ "nan", "We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P less than 0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions.", "In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the \"high\" group and nine in the \"low\" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.", "Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs.", "To determine whether there is a relationship between exposure to heparin and an increased risk of intraventricular hemorrhage (IVH), we analyzed data from a cohort of infants who had been subjects in a randomized clinical trial of umbilical artery catheter placement. Data from 862 infants who survived the first 6 days of life were used for analysis. The incidence of IVH (grades 1 through 4) was 28.6%. The mean (SD) birth weight for infants with IVH was 954 gm (247 gm) compared with 1053 gm (253 gm) among infants without IVH (p < 0.01). The mean (SD) heparin intake among infants with an IVH was 83.5 units/kg/day (48.7) compared with 59.4 units/kg/day (48.7) among infants without an IVH (p < 0.01). With the use of logistic regression modeling to adjust for a number of potentially confounding variables, including fluid intake and birth weight, we observed an odds ratio for an IVH of 1.96 (95% confidence interval = 1.32, 2.91) for infants with second through fourth quartile intakes of heparin compared with that for infants with first quartile heparin intakes. Although we cannot rule out the possibility that the observations from this model may be confounded by factors associated with the severity of illness of the infant, these data support the findings of previous reports of an association between heparin exposure and the risk for an IVH." ]
"There appears to be no evidence to support the use of low placed umbilical artery catheters. High catheters should be used exclusively."
"CD004493"
[ "11291373", "2213870", "15376818", "8812826", "2057468", "17663611", "8757573", "3437450", "9786373", "12018753", "8435601", "16201856", "12509592", "10181020", "11550729", "12079251", "12612363", "11850136", "14636795", "7673531" ]
[ "The influence of a family program on adolescent tobacco and alcohol use.", "The efficacy of social-influence prevention programs versus \"standard care\": are new initiatives needed?", "Reducing the risks of alcohol use among urban youth: three-year effects of a computer-based intervention with and without parent involvement.", "Tobacco use measurement, prediction, and intervention in elementary schools in four states: the CATCH Study.", "The Tromsø Survey: the Family Intervention study--the effect of intervention on some coronary risk factors and dietary habits, a 6-year follow-up.", "An adaptive approach to family intervention: linking engagement in family-centered intervention to reductions in adolescent problem behavior.", "Long-term follow-up of the Busselton six-year controlled trial of prevention of children's behavior disorders.", "How generalizable are the effects of smoking prevention programs? Refusal skills training and parent messages in a teacher-administered program.", "Long-term effects of nurse home visitation on children's criminal and antisocial behavior: 15-year follow-up of a randomized controlled trial.", "Tobacco and alcohol use outcomes of a school-based intervention in New Delhi.", "Evaluation of two school smoking education programmes under normal classroom conditions.", "Effects of a controlled family-based health education/counseling intervention.", "Sustaining and broadening intervention impact: a longitudinal randomized trial of 3 adolescent risk reduction approaches.", "Effects of a school-based smoking prevention program among subgroups of adolescents.", "Randomized trial of brief family interventions for general populations: adolescent substance use outcomes 4 years following baseline.", "Longitudinal substance initiation outcomes for a universal preventive intervention combining family and school programs.", "Can parents who smoke socialise their children against smoking? Results from the Smoke-free Kids intervention trial.", "A randomized controlled trial of two primary school intervention strategies to prevent early onset tobacco smoking.", "A randomized trial of a family-based smoking prevention intervention in managed care.", "Preventing escalation in problem behaviors with high-risk young adolescents: immediate and 1-year outcomes." ]
[ "This study examined a family-directed program's effectiveness in preventing adolescent tobacco and alcohol use in a general population.\n Adolescents aged 12 to 14 years and their families were identified by random-digit dialing throughout the contiguous United States. After providing baseline data by telephone interviews, they were randomly allocated to receive or not receive a family-directed program featuring mailed booklets and telephone contacts by health educators. Follow-up telephone interviews were conducted 3 and 12 months after program completion.\n The findings suggested that smoking onset was reduced by 16.4% at 1 year, with a 25.0% reduction for non-Hispanic Whites but no statistically significant program effect for other races/ethnicities. There were no statistically significant program effects for smokeless tobacco or alcohol use onset.\n The family-directed program was associated with reduced smoking onset for non-Hispanic Whites, suggesting that it is worthy of further application, development, and evaluation.", "This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to \"standard-care\" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use.", "This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents.\n Youths (N = 514, mean age 11.5 years at recruitment) were assigned randomly by community site to receive the CD-ROM intervention, the CD-ROM plus parent intervention, or no intervention. All youths completed pretest, posttest and three annual follow-up measurements. After pretesting, youths and parents received their respective interventions.\n Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes. Over time, youths in all 3 groups reported increased use of alcohol, tobacco and marijuana; youths who received the interventions reported smaller increases than control youths. At 3-year follow-up, alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths, who, in turn, reported less use than controls. Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1-, 2- and 3-year follow-ups. Marijuana use was lower for youths in either intervention than for controls at 1-, 2- and 3-year follow-ups. Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use. Finally, at the 3-year follow-up, youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group, who, in turn, reported more positive levels of family involvement than youths in the control group.\n Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents.", "The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a multistate field trial examining the effects of school environment, classroom curricula, and family intervention components in promoting the cardiovascular health of elementary school students. The purpose of this paper is to describe the CATCH tobacco use intervention and measurement, including the adoption of tobacco-free school policies.\n In this study, changes in school tobacco use policies and smoking experimentation among students were assessed. Smoking experimentation was measured in all CATCH schools when the students were in their fifth-grade year. A total of 6,527 subjects in 96 schools in California, Louisiana, Minnesota, and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior questionnaire in Spring 1994. School tobacco use policy, an important complement to classroom- and home-based prevention efforts, was promoted as part of the CATCH intervention. The degree to which such policy was implemented was measured using surveys of school officials.\n At the end of fifth grade, only 4.8% of the subjects indicated that they had experimented with tobacco. School intervention condition was not a factor in the prediction of experimentation. Those whose best friend or sibling smoked, or who had ready access to cigarettes in the home, were more likely to have experimented with smoking. In the 3 years of the study, the percentages of tobacco-free schools went up from 49.7 to 76.8%. Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention, the implementation of the tobacco-free schools' policies did vary substantially from state to state. Minnesota and Texas, with stronger state laws supporting local policy, had nearly completely smoke-free schools. In spite of a statewide tobacco control initiative, California was slower to implement school policies. Louisiana, which allows local decision making regarding smoking policy, had the most difficulty establishing a policy for all districts.\n Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels. Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district.", "While most intervention studies on coronary heart disease have focused on the high-risk person only, the present study used the family as the unit of intervention. In the study 1373 high-risk men, ages 30-54 years, were identified on the basis of high total cholesterol (TC) and/or low relative high-density lipoprotein cholesterol (HDL-C) (HDL-C/TC) following the 1979/1980 survey in Tromsø. The men and their families were randomly allocated to a control or intervention condition. The intervention families were given advice on diet, smoking, and exercise. At rescreening in 1986/1987, significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group. For children, the differences were small and mostly nonsignificant. Men, spouses, and children in the intervention group reported more favorable dietary habits than those in the control group. No differences were found in smoking or leisure time physical activity.", "This study used Complier Average Causal Effect analysis (CACE; see G. Imbens & D. Rubin, 1997) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11-17. Students were randomly assigned to a family-centered intervention (N = 998) in 6th grade and offered a multilevel intervention that included (a) a universal classroom-based intervention, (b) the Family Check-Up (selected; T. J. Dishion & K. Kavanagh, 2003), and (c) family management treatment (indicated). All services were voluntary, and approximately 25% of the families engaged in the selected and indicated levels. Participation in the Family Check-Up was predicted by 6th-grade teacher ratings of risk, youth reports of family conflict, and the absence of biological fathers from the youths' primary home. Relative to randomized matched controls, adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol, tobacco, and marijuana use and problem behavior during ages 11 through 17, along with decreased risk for substance use diagnoses and police records of arrests by age 18.", "This study reports the follow-up in 1993 of 209 adults, aged 27 to 29 years, who as children had been enrolled in a controlled trial of the prevention of children's behavior disorders. One hundred four control subjects and 105 study subjects, representing 90% of the original cohort, responded to a questionnaire detailing their present social situation and habits, educational achievements, and emotional well-being. The study subjects overall reported significantly fewer neurotic symptoms (p <0.001) than the control subjects; the study women also reported significantly fewer depressive symptoms (p <0.001). A greater proportion of the study subjects, compared with control subjects, had undertaken a university degree or diploma (p <0.013), whereas fewer of the men had attended a school of technology (p <0.049). The study women were less likely to be obese, as defined by a body mass index of 25 or more (p <0.030). The study men and women tended to smoke less than their control subjects, though significant differences were not attained. These results in the experimental group reflected the behavior patterns recorded at 6 years of age, after initial preschool interventional therapy. It appears that the initial benefit obtained from active counseling of mothers about their preschool children's behavior may be long lasting, favorably affecting the individuals' psychologic well-being, educational achievements, and social habits as adults.", "This study investigated both substantive and methodological issues associated with school-based smoking prevention programs. Substantive issues included the efficacy of a refusal skills training curriculum and of parent messages mailed to students' homes. Methodological issues included the effects of assigning classrooms versus entire schools to experimental conditions and determination of the effects of attrition on internal and external validity. Results revealed differential impact for different subgroups of adolescents. The refusal skills program produced lower rates of smoking than the control condition for students who were smokers at the pretreatment assessment but may have produced detrimental effects among males who were nonsmokers at pretest. The provision of parent messages did not affect outcome. Method of assignment (schools versus classrooms) failed to produce significant effects, and attrition did not affect internal validity. However, the above differential findings, as well as the impact of attrition on external validity, raise questions concerning the generalizability of smoking prevention programs.", "A program of home visitation by nurses has been shown to affect the rates of maternal welfare dependence, criminality, problems due to use of substances, and child abuse and neglect. However, the long-term effects of this program on children's antisocial behavior have not been examined.\n To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on children's antisocial behavior.\n Fifteen-year follow-up of a randomized trial. Interviews were conducted with the adolescents and their biological mothers or custodial parents.\n Semirural community in New York.\n Between April 1978 and September 1980, 500 consecutive pregnant women with no previous live births were recruited, and 400 were enrolled. A total of 315 adolescent offspring participated in a follow-up study when they were 15 years old; 280 (89%) were born to white mothers, 195 (62%) to unmarried mothers, 151 (48%) to mothers younger than 19 years, and 186 (59%) to mothers from households of low socioeconomic status at the time of registration during pregnancy.\n Families in the groups that received home visits had an average of 9 (range, 0-16) home visits during pregnancy and 23 (range, 0-59) home visits from birth through the child's second birthday. The control groups received standard prenatal and well-child care in a clinic.\n Children's self-reports of running away, arrests, convictions, being sentenced to youth corrections, initiation of sexual intercourse, number of sex partners, and use of illegal substances; school records of suspensions; teachers' reports of children's disruptive behavior in school; and parents' reports of the children's arrests and behavioral problems related to the children's use of alcohol and other drugs.\n Adolescents born to women who received nurse visits during pregnancy and postnatally and who were unmarried and from households of low socioeconomic status (risk factors for antisocial behavior), in contrast with those in the comparison groups, reported fewer instances (incidence) of running away (0.24 vs 0.60; P = .003), fewer arrests (0.20 vs 0.45; P = .03), fewer convictions and violations of probation (0.09 vs 0.47; P<.001), fewer lifetime sex partners (0.92 vs 2.48; P= .003), fewer cigarettes smoked per day (1.50 vs 2.50; P= .10), and fewer days having consumed alcohol in the last 6 months (1.09 vs 2.49; P = .03). Parents of nurse-visited children reported that their children had fewer behavioral problems related to use of alcohol and other drugs (0.15 vs 0.34; P = .08). There were no program effects on other behavioral problems.\n This program of prenatal and early childhood home visitation by nurses can reduce reported serious antisocial behavior and emergent use of substances on the part of adolescents born into high-risk families.", "To reduce tobacco use among adolescents.\n Thirty schools in New Delhi, India, were randomly assigned to 3 conditions: school-based and family-based intervention, school-based intervention only, or control group. Students were in the seventh grade at pretest (N = 4,776). The smoking intervention included posters, booklets, classroom activities, debates, and a signature campaign. The family intervention involved home activities. The survey measured tobacco knowledge, attitudes, offers, use, and intentions.\n Intervention students were significantly less likely than controls to have been offered, received, experimented with, or have intentions to use tobacco.\n The project had a significant impact on tobacco use.", "To assess the effectiveness of two school based smoking education projects in delaying onset of smoking behaviour and in improving health knowledge, beliefs, and values.\n Cluster randomised controlled trial of two projects taught under normal classroom conditions. Schools were allocated to one of four groups to receive the family smoking education project (FSE); the smoking and me project (SAM); both projects in sequence (FSE/SAM); or no intervention at all.\n 39 schools in Wales and England matched for size and catchment profile.\n All first year pupils in the schools were included and were assessed on three occasions (4538 before teaching (1988), 3930 immediately after teaching (1989), 3786 at one year follow up (1990)).\n Self reported smoking behaviour (backed by saliva sample) and change in relevant health knowledge, beliefs, and values.\n No consistent significant differences in smoking behaviour, health knowledge, beliefs, or values were found between the four groups. For never smokers at baseline the rate of remaining never smokers in 1990 was 74% (594/804) in the control group, 65% (455/704) in the FSE group, 70% (440/625) in the SAM group, and 69% (549/791) in the FSE/SAM group (chi 2adj = 6.1, df = 3, p = 0.1). Knowledge about effects of smoking rose in all groups from a mean score of 5.4 in 1988 to 6.4 in 1989 and 6.5 in 1990.\n More comprehensive interventions than school health education alone will be needed to reduce teenage smoking. Other measures including further restrictions on access to cigarettes and on the promotion of tobacco products need to be considered. Further research will be needed to develop effective school based health education projects, which should be formally field tested under normal conditions before widespread dissemination.", "To describe the effects of a controlled family-based health education/counseling intervention on health behaviors of children with a familial history of cardiovascular diseases (FH-CVDs).\n The intervention group (IG, n=432) received 5 counseling sessions. The control groups 1 (CG1, n=200) and 2 (CG2, n=423) received no counseling. Outcome measures comprised changes in diet, exercise, and cigarette smoking.\n The changes in the use of fats and salt, and in exercise, were more favorable in IG than in CG1 and/or CG2.\n Health education/counseling produced positive effects on diet and nutrition in particular and in part in exercise.", "To determine whether the addition of a parental monitoring intervention (Informed Parents and Children Together [ImPACT]) alone or with \"boosters\" could enhance (either broaden or sustain or both) the effect of a small group, face-to-face adolescent risk reduction intervention Focus on Kids (FOK).\n A longitudinal, randomized, community-based cohort study was conducted of 35 low-income, community-based, in-town settings. A total of 817 black youths aged 12 to 16 years at baseline were studied. After completion of baseline measures, youths were randomized to receive a face-to-face intervention alone (FOK only), a face-to-face intervention and a parental monitoring intervention (FOK plus ImPACT), or both of the above plus boosters (FOK plus ImPACT plus boosters). Risk and protective behaviors were assessed at 6 and 12 months after intervention.\n At 6 months' follow-up, youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse, sex without a condom, alcohol use, and cigarette use and marginally lower rates of \"risky sexual behavior\" compared with youths in families that were assigned to FOK only. At 12 months after intervention, rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths. With regard to the boosters delivered at 7 and 10 months, 2 risk behaviors--use of crack/cocaine and drug selling--were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters. The rates of the other risk behaviors and intentions did not differ significantly.\n The results of this randomized, controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only. At the same time, the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention.", "In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion, University of Bergen started a study of school-based interventions aiming at preventing smoking among pupils in Norwegian secondary schools. The study comprised a nationwide sample of 4441 students at 99 schools (195 classes). This panel of students is followed through annual data collections till they graduate in spring 1997. Written consensus from students and parents was obtained from 95%. Schools were systematically allocated to one of four groups: Group A, control; Group B, intervention, containing classroom program, involvement of parents and teacher courses; Group C, like B, but without teacher courses; Group D, like B, but without parental involvement. Baseline data were collected by questionnaires administered in class in November 1994 and the first follow-up survey was carried out in May 1995. At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A (control) and by 1.9 percentage points in Group B (most extensive intervention). As expected, the recruitment of smokers was higher in Groups C and D than in the ideal intervention, but lower than in the control group. Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking, physical maturity, antisocial behavior and parental smoking. The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among 'high-risk' students than among other students.", "This study examined the long-term substance use outcomes of 2 brief interventions designed for general population families of young adolescents. Thirty-three public schools were randomly assigned to 3 conditions: the 5-session Preparing for the Drug Free Years Program, the 7-session Iowa Strengthening Families Program, and a minimal contact control condition. The pretest involved 667 6th graders and their families. Assessments included multiple measures of initiation and current use of alcohol, tobacco, and marijuana. Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade. Significant intervention-control differences in initiation and current use were found for both interventions. It is concluded that brief family skills-training interventions designed for general populations have the potential to reduce adolescent substance use and thus have important public health implications.", "This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components. Thirty-six rural schools were randomly assigned to 1 of 3 conditions: (a) the classroom-based Life Skills Training (LST) and the Strengthening Families Program: For Parents and Children 10-14, (b) LST only, or (c) a control condition. Outcomes were examined 1 year after the intervention posttest, using a substance initiation index (SII) measuring lifetime use of alcohol, cigarettes, and marijuana and by rates of each individual substance. Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation. Relative reduction rates for alcohol initiation were 30.0% for the combined intervention and 4.1% for LST only.", "To evaluate Smoke-free Kids, a new home based programme to assist parents who smoke in socializing their children against smoking.\n Two year randomised controlled trial.\n At baseline, 887 adult smokers who had an abstinent child in the third grade (ages 7-8 years); 671 adults and children were retained through the 24 month follow up.\n Programme modules, newsletters, incentives, support calls.\n Anti-smoking socialisation; susceptibility to smoking.\n Of 327 parents randomised to treatment, 210 obtained adequate treatment by using at least three of five core modules. Programme efficacy analyses, which compared these parents with controls (n = 344), showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention. Two years post-baseline, children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking, and they scored significantly lower than controls on attributes that raise susceptibility to smoking. Programme effectiveness analyses compared all parents randomised to treatment (n = 327) with controls (n = 344). Treatment effects were evident for several socialisation outcomes; however, these effects were smaller and less consistent than those from the efficacy analyses. Similarly, although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility, several of these between-group differences were not significant.\n Given adequate exposure to the Smoke-free Kids programme, significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes, and significant beneficial effects were observed on children's susceptibility to smoking after two years. Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated.", "In this article, we examine the impact of two universal, grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence. The classroom-centered (CC) intervention was designed to reduce the risk for tobacco smoking by enhancing teachers' behavior management skills in first grade and, thereby, reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use. The family-school partnership (FSP) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents' child behavior management strategies. A cohort of 678 urban, predominately African-American, public school students were randomly assigned to one of three Grade 1 classrooms at entrance to primary school (age 6). One classroom featured the CC intervention, a second the FSP intervention, and the third served as a control classroom. Six years later, 81% of the students completed audio computer-assisted self-interviews. Relative to controls, a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms (26% versus 33%) (adjusted relative risk for CC/control contrast=0.57, 95% confidence interval (CI), 0.34-0.96; adjusted relative risk for FSP/control contrast=0.69, 95% CI, 0.50-0.97). Results lend support to targeting the early antecedent risk behaviors for tobacco smoking.", "Each day more than 2000 youth under age 18 become daily smokers and the age of tobacco initiation has been going down. Health care settings can partner with families to encourage parent-child interactions that prevent youth tobacco use. This study evaluates a smoking prevention intervention package for parents and children (aged 10-12) provided through their managed care organization.\n A two-arm (usual care vs intervention) randomized trial was employed. The intervention included a mailed parental smoking prevention kit, outreach follow-up telephone calls to the parent by a health educator, child materials, medical record cues for physicians to deliver prevention messages, and parent newsletter. Outcome measures were susceptibility to smoking, experimentation with smoking, and smoking in the past 30 days as assessed by 20-month follow-up surveys of children.\n A total of 4,026 families enrolled in the study. The response rate to the 20-month follow-up was 88%. There were no significant effects of the intervention on any of the primary outcomes. The intervention was associated with modest but statistically significant increases in parent-child discussions of smoking related topics.\n A minimal-intensity family-based prevention program did not significantly reduce rates of susceptibility or tobacco use among youth aged 10-12 at baseline and 11 to 14 at follow-up. Development and evaluation of innovative approaches to tobacco use prevention must continue, despite our disappointing results. Parents and health care systems are too important to abandon as channels for prevention messages.", "The study tested alternative intervention strategies to reduce escalation in problem behaviors among high-risk young adolescents (11 to 14 years old). A total of 158 families with young adolescents (male and female) participated in this study. Of these, 119 families were randomly assigned to 1 of the following intervention conditions: (a) parent focus, (b) teen focus, (c) parent and teen focus, (d) self-directed change (materials only). In addition, 39 families of young adolescents were recruited as a quasi-experimental control. Parent focus and teen focus interventions resulted in immediate beneficial effects in observed and reported family conflict. The parent intervention conditions showed immediate beneficial effects on behavior problems at school. Longitudinal trends suggest that the parent focus condition may reduce subsequent tobacco use, compared with all other approaches. Interventions that aggregated high-risk youths into groups, however, showed the highest escalations in tobacco use and problem behavior at school, beginning at termination and persisting to follow-up. These findings are discussed with respect to the need to re-evaluate strategies that aggregate high-risk youths into intervention programs and focus more on strategies to engage parents in prevention." ]
"Some well-executed RCTs show family interventions may prevent adolescent smoking, but RCTs which were less well executed had mostly neutral or negative results. There is thus a need for well-designed and executed RCTs in this area."
"CD003734"
[ "5109955" ]
[ "Reduction of young driver crashes in a controlled pilot study: two-year follow-up in one Michigan high school." ]
[ "nan" ]
"This systematic review provides no evidence that post-licence driver education is effective in preventing road traffic injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic offences, this may be due to selection biases or bias in the included trials. Because of the large number of participants included in the meta-analysis (close to 300,000 for some outcomes) we can exclude, with reasonable precision, the possibility of even modest benefits."
"CD000296"
[ "8889459", "12135030", "12548062", "16733496", "9301500", "8078529", "9663720", "8078530", "15095852", "9753485", "10961590", "11922560", "7605858" ]
[ "Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn's disease. German/Austrian Budesonide Study Group.", "Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States.", "A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease.", "Beclomethasone dipropionate for the treatment of mild-to-moderate Crohn's disease: an open-label, budesonide-controlled, randomized study.", "Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group.", "Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.", "Bone turnover during short-term therapy with methylprednisolone or budesonide in Crohn's disease.", "A comparison of budesonide with prednisolone for active Crohn's disease.", "Budesonide versus prednisolone for the treatment of active Crohn's disease in children: a randomized, double-blind, controlled, multicentre trial.", "Budesonide versus prednisone in the treatment of active Crohn's disease. The Israeli Budesonide Study Group.", "Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.", "Budesonide and mesalazine in active Crohn's disease: a comparison of the effects on quality of life.", "Budesonide and prednisolone suppress peripheral blood natural killer cells in Crohn's disease." ]
[ "Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred).\n This was a prospective multicentre, randomized, double-blind, double-dummy study.\n A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks.\n Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015).\n Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.", "Budesonide controlled ileal release (CIR) capsules deliver budesonide, a glucocorticosteroid with high topical and low systemic activity, to the distal ileum and the proximal colon. In four previous controlled trials in Crohn's disease, remission rates ranged from 51% to 69%. We sought to evaluate the efficacy and safety of this drug in a population of patients in the United States with Crohn's disease.\n In this multicenter, double blind, randomized trial, 200 patients in the United States with mild to moderate Crohn's disease (Crohn's Disease Activity Index [CDAI] between 200 and 450) involving the distal ileum and/or ascending colon received 9 mg of budesonide CIR once daily, 4.5 mg b.i.d., or placebos for 8 wk. The primary outcome was remission defined by a CDAI of 150 or less.\n Remission was achieved in 48%, 53%, and 33% with 9 mg once daily, 4.5 mg b.i.d., and placebos, respectively, after 8 wk of treatment. Differences between the groups were not significant. The differences in mean change from baseline CDAI between the combined budesonide and placebo groups was significant (p < 0.05). There was no difference in observed adverse events between treatment groups, although a modest decrease in plasma cortisol levels was observed relative to the placebo (p < 0.01).\n Treatment of symptomatic Crohn's disease with budesonide CIR capsules (9 mg daily) was safe, and remission rates were similar to those achieved in previous trials. Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo.", "Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease.\n A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease.\n Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01).\n Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.", "Budesonide is a steroid with low systemic effect and high effectiveness in the treatment of Crohn's Disease (CD). Beclomethasone dipropionate (BDP) is also a steroid with the same systemic effects, but it has been never investigated in CD.\n To evaluate the effectiveness and tolerability of BDP versus budesonide in treating CD, we enrolled 30 consecutive patients affected by mild-to-moderate non-fistulizing, non-obstructive Crohn's disease (CDAI < or = 250) (13 M and 17 F, mean age: 33.4 years, range: 16-71 years) in whom this diagnosis was made for the first time. The patients were randomly treated for 8 weeks with budesonide 9 mg/day (group A, 15 patients) or with BDP 10 mg/day (group B, 15 patients).\n Of group A patients, 13/14 (on intention to treat (i-t-t): 86.67%) showed response to budesonide and 10/14 (on i-t-t.: 66.66%) were in remission after 8 weeks of treatment. In group B patients, 10/14 (on i-t-t: 66.66%) showed response to BDP and 8/14 (on i-t-t: 53.33%) were in remission after 8 weeks of treatment (p<0.001). Budesonide was also faster in the time to obtain symptomatic remission (p=n.s.) and was better in improving IBDQL (p<0.05). Regarding side effects, two group A patients (6.66%) and three group B patients (10%) experienced mild-to-moderate side effects which were transitory and did not require any specific treatment or stopping the treatment.\n BDP seems to be less effective than budesonide in treating CD, probably due to better the pharmacokinetic properties of budesonide.", "The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.\n To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon.\n One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less.\n After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023).\n Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.", "Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon.\n In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index.\n After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects.\n In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.", "Glucocorticosteroids are used frequently for the treatment of relapses of Crohn's disease.\n To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial.\n Twenty-nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering.\n Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 +/- 2.6 to 20.4 +/- 2.0 ng/mL. P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 +/- 3.1 to 33.0 +/- 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group.\n Short-term methylprednisolone therapy impairs osteoblast activity in patients with Crohn's disease whereas budesonide does not.", "Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low.\n We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week.\n At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks.\n Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.", "Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease.\n Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks).\n The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25).\n Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission.", "Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon.\n Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded.\n One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks.\n BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.", "Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.", "Controlled ileal release budesonide and slow release mesalazine are both used to treat mild to moderate active Crohn's disease, although data show that budesonide is more effective in inducing remission. When comparing different treatment options, the effects of agents on health-related quality of life must be considered as well as efficacy. In this study, we sought to compare the effects of budesonide and mesalazine on the health-related quality of life of patients with active Crohn's disease.\n The study included 182 patients with Crohn's Disease Activity Index scores between 200 and 400. Patients were randomized in a double blind, double dummy, multicenter study to receive 9 mg of budesonide, once daily (n = 93), or 2 g of mesalazine, b.i.d. (n = 89), for 16 wk. Quality of life was assessed at baseline and after 2, 4, 8, 12, and 16 wk of treatment using the Psychological General Well-Being index. In addition, a physician's global evaluation was used to assess how symptoms affected patients' normal activities.\n Patients treated with budesonide experienced significantly greater improvement in Psychological General Well-Being scores than the group treated with mesalazine after 2, 8, 12, and 16 wk. All components of this index showed greater improvements in the budesonide-treated group than in the mesalazine group at 12 and 16 wk. The physician's global evaluation showed significantly greater improvements in the budesonide group than in the mesalazine group at all visits.\n Budesonide (9 mg once daily) improves health-related quality of life to a greater extent than mesalazine (2 g b.i.d.) in patients with mild to moderate active Crohn's disease.", "To study the effect of oral budesonide and prednisolone on peripheral blood natural killer (NK) cell activity in patients with active ileocaecal Crohn's disease (Crohn's disease activity index, CDAI > or = 200).\n One group of patients was treated for 10 weeks with oral budesonide (n = 9; 9 mg/day), and another group of patients for the same period with prednisolone (n = 9; 40 mg/day). Budesonide was tapered to 6 mg/day after 8 weeks and prednisolone after 2 weeks to 5 mg/day in the last week. Before treatment, and at 2, 4 and 10 weeks of treatment, natural killer cell activity was determined with a 51Cr release assay, and the number of CD16+ NK cells by Fluorescence activated cell sorter (FACS) analysis.\n Budesonide, as well as prednisolone treatment, significantly decreased natural killer cell activity at weeks 2 and 4. This decrease was found to be accompanied by a similar decrease in the number of CD16+ NK cells. At 10 weeks, natural killer cell activity had almost returned to pre-treatment levels in the budesonide group and was significantly higher than pre-treatment levels in the prednisolone group. Disease activity was significantly decreased in all patients at week 2 until the end of the trial period.\n Both budesonide and prednisolone treatment suppress peripheral blood natural killer cell activity of patients with active ileocaecal Crohn's disease by decreasing the numbers of CD16+ NK cells in the circulation." ]
"Budesonide is more effective than placebo or mesalamine for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression is lower."
"CD006181"
[ "2498657" ]
[ "A randomized, controlled trial of very early prophylactic ligation of the ductus arteriosus in babies who weighed 1000 g or less at birth." ]
[ "We speculated that prophylactic ligation of the ductus arteriosus would reduce mortality and morbidity in very-low-birth-weight infants. To test this hypothesis, we randomly assigned 84 babies who weighed 1000 g or less at birth and required supplemental oxygen either to receive standard treatment (n = 44) or to undergo prophylactic surgical ligation of the ductus arteriosus on the day of birth (n = 40). The ductus was ligated in babies in the control group only if the shunt was hemodynamically important. All the babies were followed for one year. The incidence of necrotizing enterocolitis was reduced in the group that underwent prophylactic ligation (3 of 40 [8 percent]) as compared with the control group (13 of 44 [30 percent]; P = 0.002). The frequency of death, bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage was similar in both groups. Because early enteral feeding may have increased the incidence of necrotizing enterocolitis, we analyzed separately the babies who were fed early. Among the infants who were fed within 14 days of birth, those who underwent prophylactic ligation had a lower incidence of necrotizing enterocolitis (1 of 11 [9 percent]) than those who did not (13 of 24 [54 percent]; P = 0.001). Within the control group, the infants who were fed within 14 days of birth and whose ductus was ligated for medical reasons within 5 days of birth had a lower incidence of necrotizing enterocolitis (2 of 10 [20 percent]) than those whose ductus was ligated later or not at all (11 of 14 [79 percent]; P = 0.004). We conclude that early surgical closure of the ductus arteriosus reduces the risk of necrotizing enterocolitis in infants of very low birth weight who require supplemental oxygen." ]
"Prophylactic surgical ligation of the PDA did not decrease mortality or BPD in ELBW infants. A significant reduction of stage II or III NEC was noted. Based on the current evidence, the high rate of spontaneous closure, availability of effective safe medical therapies, and the potential short and long-term complications of surgical ligation, the use such prophylactic surgical therapy is not indicated in the management of the preterm infants."
"CD002818"
[ "14759641", "2730380", "7501140", "2972270", "2889518" ]
[ "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.", "Amantadine treatment of fatigue associated with multiple sclerosis.", "Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.", "Amantadine, fatigue, and multiple sclerosis.", "A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group." ]
[ "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.", "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 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.", "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.", "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." ]
"The efficacy of amantadine in reducing fatigue in people with MS is poorly documented, as well as its tolerability. It is advisable to: (1) improve knowledge on the underlying mechanisms of MS-related fatigue; (2) achieve an agreement on accurate, reliable and responsive outcome measures of fatigue; (3) perform good quality RCTs."
"CD007182"
[ "7654268", "3484773", "3501750", "10190377", "12604518", "2802557", "10225575", "2188590", "10212779", "3158277", "7928829", "8449579", "215795", "15728165", "12195873", "3492486", "893246", "3157008" ]
[ "Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women.", "Randomized study of single-dose, three-day, and seven-day treatment of cystitis in women.", "Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis.", "A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Ciprofloxacin Urinary Tract Infection Group.", "Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women.", "Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis.", "A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.", "Randomized, controlled trial of a 10-day course of amifloxacin versus trimethoprim-sulfamethoxazole in the treatment of acute, uncomplicated urinary tract infection. Amifloxacin Multi-Center Trial Group.", "Comparative study of single-dose and three-day therapy for acute uncomplicated cystitis.", "Norfloxacin versus trimethoprim-sulfamethoxazole in the therapy of uncomplicated, community-acquired urinary tract infections.", "Nitrofurantoin modified release versus trimethoprim or co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice.", "Cefuroxime axetil versus ofloxacin for short-term therapy of acute uncomplicated lower urinary tract infections in women.", "Comparative controlled clinical trial of pivmecillinam and nalidixic acid in patients with acute simple urinary tract infections.", "Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial.", "Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.", "Comparison of ciprofloxacin and co-trimoxazole in the treatment of uncomplicated urinary tract infection in women.", "A comparison of pivmecillinam and cotrimoxazole in the treatment of simple cystitis in general practice.", "Efficacy of norfloxacin in urinary tract infection biological effects on vaginal and fecal flora." ]
[ "To determine the efficacy, safety, and costs associated with four different 3-day regimens for the treatment of acute uncomplicated cystitis in women.\n A prospective randomized trial with a cost analysis.\n Women with acute cystitis attending a student health center.\n Treatment with 3-day oral regimens of trimethoprim-sulfamethoxazole, 160 mg/800 mg twice daily, macrocrystalline nitrofurantoin, 100 mg four times daily, cefadroxil, 500 mg twice daily, or amoxicillin, 500 mg three times daily.\n Six weeks after treatment, 32 (82%) of 39 women treated with trimethoprim-sulfamethoxazole were cured compared with 22 (61%) of 36 treated with nitrofurantoin (P = .04 vs trimethoprim-sulfamethoxazole), 21 (66%) of 32 treated with cefadroxil (P = .11 vs trimethoprim-sulfamethoxazole), and 28 (67%) of 42 treated with amoxicillin (P = .11 vs trimethoprim-sulfamethoxazole). Persistence of significant bacteriuria was less common with trimethoprim-sulfamethoxazole (3%) and cefadroxil (0%) compared with nitrofurantoin (16%; P = .05 vs trimethoprim-sulfamethoxazole) and amoxicillin (14%; P = .11 vs trimethoprim-sulfamethoxazole). Persistence of bacteriuria was associated with amoxicillin-resistant strains in the amoxicillin group but nitrofurantoin-susceptible strains in the nitrofurantoin group. Trimethoprim-sulfamethoxazole was more successful in eradicating Escherichia coli from rectal cultures soon after therapy and from urethral and vaginal cultures at all follow-up visits compared with the other treatment regimens. Adverse effects were reported by 16 (35%) of 46 patients receiving trimethoprim-sulfamethoxazole, 18 (43%) of 42 receiving nitrofurantoin, 12 (30%) of 40 receiving cefadroxil, and 13 (25%) of 52 receiving amoxicillin. The mean costs per patient were less with trimethoprim-sulfamethoxazole ($114) and amoxicillin ($131) compared with nitrofurantoin ($155) and cefadroxil ($155).\n A 3-day regimen of trimethoprim-sulfamethoxazole is more effective and less expensive than 3-day regimens of nitrofurantoin, cefadroxil, or amoxicillin for treatment of uncomplicated cystitis in women. The increased efficacy of trimethoprim-sulfamethoxazole is likely related to its antimicrobial effects against E coli in the rectum, urethra, and vagina.", "We evaluated the following five treatment regimens for acute cystitis in nonpregnant women: cefadroxil, 1,000 mg single-dose; cefadroxil, 500 mg twice a day for three days; cefadroxil, 500 mg twice a day for seven days; trimethoprim-sulfamethoxazole (TMP-SMZ), 320-1,600 mg single-dose, and TMP-SMZ, 160-800 mg twice a day for three days. At four weeks after the end of treatment, 25%, 58%, 70%, 65%, and 88% of patients, respectively, remained cured of infection. The results indicated that three-day treatment (1) might improve cure rates (over single-dose), (2) would reduce incidence of relapse (vs. single-dose), and (3) may be as curative as seven-day treatment. The results of the antibody-coated bacteria test did not predict treatment failure or relapse.", "The clinical and bacteriological efficacy and adverse reactions of ofloxacin vs trimethoprim-sulphamethoxazole were investigated in a double-blind, randomised study in 250 female patients (125 in each group) with acute, uncomplicated lower urinary tract infections. The dosages of ofloxacin and trimethoprim-sulphamethoxazole were 100mg and 160mg + 800mg twice daily, respectively. The duration of therapy was 3 days. 81% of the patients had significant bacteriuria. Escherichia coli was isolated in 76% and Staphylococcus saprophyticus in 11% of the infections. The bacteriological elimination, clinical cure and improvement rates of the evaluable patients on ofloxacin treatment were 92 and 95%, respectively. The corresponding figures on trimethoprim-sulphamethoxazole therapy were 88 and 90%. Adverse reactions were clinically unimportant, and none of the patients had to stop treatment. Mild and transient side effects, mainly from the gastrointestinal tract, central nervous system and skin, were reported by 19 and 22% of the patients in the ofloxacin and trimethoprim-sulphamethoxazole groups, respectively. None of the differences in clinical and bacteriological efficacy and side effects of ofloxacin vs trimethoprim-sulphamethoxazole were statistically significant. Ofloxacin appears to be an appropriate antibiotic for short term therapy of acute, uncomplicated, lower urinary tract infections, comparing favourably with trimethoprim-sulphamethoxazole treatment in this study.", "Bladder infections are very common in otherwise healthy women, and short-course antimicrobial treatment appears effective for many episodes of cystitis. This study reports the results of short-course ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole therapy.\n We performed a randomized, double-blind study of the efficacy and safety of a 3-day course of oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute, uncomplicated, symptomatic lower urinary tract infection.\n A total of 866 patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of treatment (229 treated with ciprofloxacin, 228 treated with trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent reason for exclusion was the failure to identify a pretreatment pathogen. The most commonly isolated pathogen was Escherichia coli (81%). Eradication of the pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93% of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection) were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13% in the ofloxacin treatment group. Clinical success at the end of therapy was 93% in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the ofloxacin treatment groups. The frequency of all adverse events was 31% for ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin-treated patients (P = 0.03). Premature discontinuation of study drug due to an adverse event was more common in trimethoprim/sulfamethoxazole-treated patients (n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P = 0.02).\n Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole had similar efficacy when given for 3 days to treat acute, symptomatic, uncomplicated lower urinary tract infection in women.", "One hundred sixty-three women with uncomplicated acute lower urinary tract infections were included in a multicenter randomized study comparing cefpodoxime-proxetil (one 100-mg tablet twice daily) with trimethoprim-sulfamethoxazole (one double-strength tablet [160/800 mg] twice daily) for 3 days. A total of 30 women in both arms were excluded from the study for various reasons. At 4 to 7 days after the discontinuation of therapy, 62 of 63 (98.4%) cefpodoxime-proxetil recipients and 70 of 70 (100%) trimethoprim-sulfamethoxazole patients were clinically cured and demonstrated bacteriological eradication, respectively. At 28 days after treatment, 48 of 55 (87.3%) and 43 of 50 (86%) cefpodoxime-proxetil recipients as well as 51 of 60 (85%) and 42 of 50 (84%) trimethoprim-sulfamethoxazole recipients were clinically cured and demonstrated bacteriological eradication, respectively. Independently of the prescribed regimen, a significant difference (P < 0.001) in failure rates was observed only for patients with a previous history of three or more episodes of acute cystitis per year. With the exception of one patient in the trimethoprim-sulfamethoxazole arm who discontinued therapy because of gastrointestinal pain, both antimicrobials were well tolerated. In conclusion, cefpodoxime-proxetil treatment for 3 days was as safe and effective as trimethoprim-sulfamethoxazole for 3 days for the treatment of uncomplicated acute cystitis in women.", "We compared the safety and efficacies of ofloxacin and trimethoprim-sulfamethoxazole for the treatment of acute uncomplicated cystitis in women enrolled in a multicenter study. Data from three centers were combined for this report because the study design and study populations were identical, and patients were enrolled within an 18-month period. Cure rates for evaluable patients 4 weeks after treatment were high for all regimens: ofloxacin (200 mg) twice daily for 3 days, 22 of 25 (88%) cured; ofloxacin (200 mg) twice daily for 7 days, 42 of 49 (86%) cured; ofloxacin (300 mg) twice daily for 7 days, 25 of 25 (100%) cured; and trimethoprim-sulfamethoxazole (160/800 mg) twice daily for 7 days, 46 of 52 (88%) cured. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during and 1 week after treatment. Both ofloxacin and trimethoprim-sulfamethoxazole markedly reduced vaginal colonization with E. coli during and 4 weeks after therapy. Emergence of resistant coliforms in rectal flora was found in 5 (19%) of 27 patients treated with trimethoprim-sulfamethoxazole but none of 50 ofloxacin-treated patients who were studied (P = 0.004). Adverse effects were equally common among the four treatment groups. We conclude that 3 to 7 days of ofloxacin is as safe and effective as trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women and that ofloxacin effectively reduces the fecal and vaginal reservoirs of coliforms in such patients.", "The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4-10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = -20.6%, -3.9%) and nitrofurantoin (82%; 95% CL = -17.1%, -0.9%). Clinical resolution 4-10 days after therapy and at the 4-6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P = 0.093) among the three drug regimens, although co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P < or = 0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P < or = 0.01).", "We conducted a randomized controlled trial of orally administered amifloxacin versus trimethoprimsulfamethoxazole (TMP-SMX) as treatments of acute uncomplicated urinary tract infection in women. Amifloxacin at a dosage of 200 mg twice a day appeared as safe and effective as TMP-SMX, but amifloxacin at 400 mg twice a day tended to cause adverse events more frequently than did TMP-SMX.", "To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.", "In a prospective, randomized trial, norfloxacin (400 mg perorally, twice a day) was compared with trimethoprim-sulfamethoxazole (160-800 mg perorally, twice a day) in 45 patients with uncomplicated urinary tract infections. Escherichia coli was the most common isolate. Infections due to Enterobacter spp., Proteus mirabilis, Pseudomonas spp., and Staphylococcus spp. were also treated. Norfloxacin was equivalent in effectiveness and safety to trimethoprim-sulfamethoxazole, with a cure rate of 91% at the 5- to 9-day posttherapy visit and 88% at the 4- to 6-week posttherapy visit. It was well tolerated and had a low incidence of side effects.", "A total of 538 patients from 45 different general practice centres across the UK was admitted to an open study and randomized to one of the following treatment groups: nitrofurantoin modified release (MR) 100 mg bd, trimethoprim 200 mg bd or co-trimoxazole 960 mg bd. Each patient received seven days of medication. Clinical cure, defined as relief from symptoms at visit 2, occurred in 87.2% of the patients treated with nitrofurantoin MR, 84.5% of the co-trimoxazole group and 86.5% of the trimethoprim group. The bacteriological cure rate for nitrofurantoin MR was comparable to co-trimoxazole at 82.3% and 83.2%, respectively, with trimethoprim the lowest at 76.8%. Whilst the cure rate for Escherichia coli infection was similar, 81.5% cured with nitrofurantoin MR, 82.5% with co-trimoxazole and 78.4% by trimethoprim, for non-E. coli pathogens nitrofurantoin MR was equivalent to co-trimoxazole with 86.7% cure but higher than trimethoprim at 72.0%. In-vitro sensitivity to all pathogens isolated at baseline was very high for nitrofurantoin at 96.1%, significantly higher than either co-trimoxazole or trimethoprim at 87.5% (P < 0.01). The test drugs were equally well tolerated with 28 patients (15.7%) reporting adverse events with nitrofurantoin MR, 28 (15.5%) with co-trimoxazole and 28 (15.6%) with trimethoprim. However, nitrofurantoin MR showed fewer patients with drug-related adverse events (5.6%) as judged by the investigator, compared to co-trimoxazole (8.8%) or trimethoprim (7.3%). (ABSTRACT TRUNCATED AT 250 WORDS)", "In a multicentre study 163 women with acute lower urinary tract infection were treated orally with either 125 mg cefuroxime axetil or 100 mg ofloxacin twice daily for three days. Both antimicrobial agents were generally well tolerated. Four patients in the group treated with cefuroxime axetil and two in the group treated with ofloxacin experienced adverse events. Clinical cure and improvement were registered in 56 of 66 (84.8%) and 59 of 62 (95.2%) of the evaluable patients treated with cefuroxime axetil and ofloxacin, respectively. Seven to nine days after therapy, bacteriuria (CFU < 10(3)/ml) had been eliminated in 53 of 66 (80.3%) and 57 of 64 (89.1%) of the evaluable patients receiving cefuroxime axetil and ofloxacin, respectively. The results were not statistically significantly different (p > 0.1). Pathogens present at baseline were eliminated by up to an MIC of 16 mg/l of cefuroxime axetil, independent of susceptibility to this agent. There was no difference with regard to efficacy and tolerance between patients treated with cefuroxime axetil and those treated with ofloxacin. On the basis of the MICs of six antimicrobial agents (cefuroxime, ofloxacin, cefadroxil, ampicillin, trimethoprim with and without sulfamethoxazole) determined for the pathogens isolated prior to therapy, resistance rates were lowest for cefuroxime (2.2%) and ofloxacin (3.4%).", "We performed a controlled double-blind clinical study with PMPC to investigate its therapeutic usefulness in acute simple cystitis in comparison with NA, with the results as follows: 1. In both treatment groups, PMPC proved to be remarkably more active (MIC) than NA against the bacterial isolates tested in vitro. 2. PMPC, administered in dosis (200 mg per day) one-tenth those of NA (2,000 mg per day), produced a greater improvement (therapeutic effects) than NA. 3. Side-effects were apparently less frequent with PMPC, as compared to NA. The results indicate a remarkable usefulness of PMPC in the treatment of acute simple cystitis.", "The high prevalence of resistance to trimethoprim-sulfamethoxazole and other antimicrobials among Escherichia coli causing acute cystitis in women has led to increased use of alternative antibiotics. One such antibiotic, amoxicillin-clavulanate, has not been well studied.\n To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate to that of a 3-day regimen of ciprofloxacin in the treatment of acute cystitis in women. The primary study hypothesis was that the amoxicillin-clavulanate and ciprofloxacin treatment groups would differ in clinical cure.\n Randomized, single-blind treatment trial of 370 women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis and a urine culture with at least 10(2) colony-forming units of uropathogens per milliliter from a university student health center or a health maintenance organization.\n Women were randomly assigned to receive amoxicillin-clavulanate (500 mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for 3 days and were followed up for 4 months.\n The main outcome measure was clinical cure. Secondary study outcomes of interest were microbiological cure and vaginal E coli colonization at the 2-week follow-up visit.\n Clinical cure was observed in 93 (58%) of 160 women treated with amoxicillin-clavulanate compared with 124 (77%) of 162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate was not as effective as ciprofloxacin even among women infected with strains susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin-clavulanate group vs 114 [77%] of 149 women in the ciprofloxacin group; P = .004). The difference in clinical cure rates occurred almost entirely within the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared with 153 (95%) of 161 women treated with ciprofloxacin (P<.001). At this visit, 45% of women in the amoxicillin-clavulanate group compared with 10% in the ciprofloxacin group had vaginal colonization with E coli (P<.001).\n A 3-day regimen of amoxicillin-clavulanate is not as effective as ciprofloxacin for the treatment of acute uncomplicated cystitis, even in women infected with susceptible strains. This difference may be due to the inferior ability of amoxicillin-clavulanate to eradicate vaginal E coli, facilitating early reinfection.", "Pivmecillinam is a unique beta-lactam antimicrobial that has been used for the treatment of acute uncomplicated urinary infection for > 20 y. Since this agent was introduced, the quinolone antimicrobials have become widely used for the same indication. This study compared the efficacy of a 3-d regimen of pivmecillinam 400 mg b.i.d. with norfloxacin 400 mg b.i.d. Women aged between 18 and 65 y presenting with symptoms of acute cystitis of < 7 d duration were eligible for enrollment; 483 were randomized to receive pivmecillinam and 471 to receive norfloxacin. In each group, 30% of women had negative urine cultures prior to therapy. Bacteriologic cure at early post-therapy follow-up was achieved in 222/298 (75%) pivmecillinam patients and 276/302 (91%) norfloxacin patients [p < 0.001; 95% confidence interval (CI) 12.0-21.8]. Clinical cure/improvement at Day 4 following initiation of therapy was observed in 434/457 (95%) women who received pivmecillinam and 425/442 (96%) who received norfloxacin (p = 0.39; 95% CI 1.5-3.9). Early post-therapy (11 +/- 2 d) clinical cure was achieved in 360/437 women (82%) who received pivmecillinam and 381/433 (88%) who received norfloxacin (p = 0.019; 95% CI 0.9-10.3). In women aged < or = 50 y, early clinical cure rates were 294/351 (84%) for pivmecillinam and 299/340 (88%) for norfloxacin (p = 0.11; 95% CI 1.0-9.4). Adverse effects were similar for both regimens, and there was no evidence of the emergence of organisms of increasing resistance with therapy. Short-course therapy with norfloxacin was superior to that with pivmecillinam in terms of bacteriologic outcome, although differences in clinical outcome were less marked. In conclusion, short-course therapy with pivmecillinam is an effective empirical treatment for pre-menopausal women.", "Sixty-five women with uncomplicated urinary tract infection were evaluated in a prospective, randomized, double blind study comparing ciprofloxacin (250 mg twice daily for ten days) with co-trimoxazole (160 mg trimethoprim and 800 mg sulphamethoxazole twice daily for ten days). Results were analysed with respect to eradication of the urinary tract pathogen, resolution of clinical symptoms, incidence of relapse, and incidence of adverse effects. Among the 31 women who received ciprofloxacin, there was eradication of the micro-organism and complete resolution of clinical symptoms in 100% five to nine days after completion of therapy. Among the 34 patients who received co-trimoxazole, there was eradication in 94% and clinical resolution in 91%. Of the ciprofloxacin-treated women 6.5% (2/31) relapsed compared with 18% (6/34) of co-trimoxazole-treated women. Overall cure rates for 65 patients were 93.5% and 82.3% for ciprofloxacin and co-trimoxazole (difference not statistically significant), respectively. A statistically significant (P less than 0.05) increase in adverse side effects was noted in patients treated with co-trimoxazole. Based upon preliminary data it appears that ciprofloxacin is as effective and less toxic than co-trimoxazole for treatment of uncomplicated urinary tract infection in women.", "Pivmecillinam was compared with cotrimoxazole in the treatment of uncomplicated bacterial cystitis in general practice. Similar bacteriological cure rates were obtained with the two treatments. Although micrococci were judged resistant to pivmecillinam by the disc sensitivity method used, cystitis attributed to these organisms and to resistant strains of Proteus mirabilis responded as readily as those due to apparently sensitive Gram-negative bacteria. Pivmecillinam was well tolerated.", "Forty women with uncomplicated urinary tract infections were assigned randomly to receive 400 mg. norfloxacin or 160 mg. trimethoprim and 800 mg. sulfamethoxazole twice daily for 10 days. Of the 20 patients receiving norfloxacin none had bacteriuria during or 7 days after therapy and 5 patients were reinfected within 6 weeks of therapy discontinuation. Of the 20 patients receiving trimethoprim-sulfamethoxazole therapy 1 presented with a strain resistant to trimethoprim-sulfamethoxazole and was excluded from the study. The remaining 19 patients were uninfected during and 7 days after therapy, and 6 patients were reinfected 6 weeks after therapy. All documented recurrences were caused by bacteria sensitive to the initial therapeutic agent. Anal and vaginal Enterobacteriaceae maintained their sensitivity to norfloxacin. One patient on trimethoprim-sulfamethoxazole presented with and 2 patients acquired resistant anal and vaginal Enterobacteriaceae. No adverse reactions occurred in either treatment group. Norfloxacin was as effective and safe as trimethoprim-sulfamethoxazole without emergence of resistant bacteria associated with trimethoprim-sulfamethoxazole." ]
"No differences were observed between the classes of antimicrobials included in this review for the symptomatic cure of acute uncomplicated UTI. Fluoroquinolones proved more effective than beta-lactams for the short-term bacteriological outcome, probably with little clinical significance. Individualised treatment should take into consideration the predictable susceptibility of urinary pathogens in local areas, possible adverse events and resistance development, and patient preference."
"CD009148"
[ "10561655", "12748513", "3524234", "8169910", "2358916", "6379529", "8399011", "2372330" ]
[ "Comparison of visual and computerized interpretation of nonstress test results in a randomized controlled trial.", "Screening for fetal well-being in a high-risk pregnant population comparing the nonstress test with umbilical artery Doppler velocimetry: a randomized controlled clinical trial.", "Fetal acoustic stimulation testing. II. A randomized clinical comparison with the nonstress test.", "Comparison of the acoustic stimulation test with nonstress test. A randomized, controlled clinical trial.", "Vibroacoustic stimulation and fetal heart rate in nonstress tests.", "Fetal biophysical profile score and the nonstress test: a comparative trial.", "The effect of introduction of umbilical Doppler recordings to obstetric practice.", "Effect of vibratory acoustic stimulation on the duration of fetal heart rate monitoring tests." ]
[ "This study tested the null hypothesis that the number of fetal surveillance tests and perinatal outcomes would not differ statistically between pregnancies randomized to visual or computerized interpretation of antepartum nonstress test results.\n A prospective, randomized controlled trial was conducted, which required a sample size of 404 patients. By using a random-number table with assignment codes concealed in opaque envelopes, half of the patients were randomized to computerized interpretation of nonstress test results and half to standard visual interpretation of nonstress test results. The amount of antepartum testing and the perinatal outcome were measured and compared between the groups. Logistic regression analysis was used to control for maternal risk factors while morbidity differences between the 2 groups were assessed.\n The 2 randomized groups were similar at baseline, but the computerized interpretation group had significantly fewer biophysical profiles compared with the visual interpretation group (1.3 +/- 1.8 vs 1.9 +/- 2.1; P =.002). The patients in the computerized interpretation group spent less time per test than patients in the visual interpretation group (12 vs 20 minutes; P =.038). After the 5 pregnancies with congenital anomalies were excluded, the overall perinatal outcome was similar in the 2 groups. The computerized interpretation group, however, had a slightly lower proportion of infants who required >/=2 days of neonatal intensive care (7.4% vs 12.4%; P =.086; odds ratio, 0.56; 95% confidence interval, 0.29-1.09). The average number of neonatal intensive care days was also slightly lower in the computerized interpretation group (0.4 vs 0.9; P =.105). Neither of these variables was statistically significant.\n Computerized interpretation of nonstress test results is associated with fewer additional fetal surveillance examinations, less time spent in testing, and a similar length of stay in the neonatal intensive care unit compared with standard visual interpretation.", "The purpose of this study was to evaluate the ability of two different modes of antepartum fetal testing to screen for the presence of peripartum morbidity, as measured by the cesarean delivery rate for fetal distress in labor.\n Over a 36-month period, all patients who were referred to the Fetal Assessment Unit at BC Women's Hospital because of a perceived increased fetal antepartum risk at a gestational age of > or =32 weeks of gestation were approached to participate in this study. Fetal surveillance of these women was allocated randomly to either umbilical artery Doppler ultrasound testing or nonstress testing as a screening test for fetal well-being. If either the umbilical artery Doppler testing or the nonstress testing was normal, patients were screened subsequently with the same technique, according to study protocol. When the Doppler study showed a systolic/diastolic ratio of >90th percentile or the nonstress testing was equivocal (ie, variable decelerations), an amniotic fluid index was performed, as an additional screening test. When the amniotic fluid index was abnormal (<5th percentile), induction and delivery were recommended. When the Doppler study showed absent or reversed diastolic blood flow or when the nonstress test result was abnormal, induction and delivery were recommended to the attending physician. Statistical comparisons between groups were performed with an unpaired t test for normally distributed continuous variables and chi(2) test for categoric variables.\n One thousand three hundred sixty patients were assigned randomly to groups in the study; 16 patients were lost to follow up. Six hundred forty-nine patients received Doppler testing and 691 received nonstress testing. The mean number of visits for the Doppler test and nonstress test groups was two versus two, respectively. The major indications for fetal assessment included postdates (43%), decreased fetal movement (22%), diabetes mellitus (11%), hypertension (10%), and intrauterine growth restriction (7%). The incidence of cesarean delivery for fetal distress was significantly lower in the Doppler group compared with the nonstress testing group (30 [4.6%] vs 60 [8.7%], respectively; P <.006). The greatest impact on the reduction in cesarean deliveries for fetal distress was seen in the subgroups in which the indication for testing was hypertension and suspected intrauterine growth restriction.\n Umbilical artery Doppler as a screening test for fetal well-being in a high-risk population was associated with a decreased incidence of cesarean delivery for fetal distress compared to the nonstress testing, with no increase in neonatal morbidity.", "Antepartum fetal heart rate testing, specifically the nonstress test, is of accepted value in the antenatal surveillance of high-risk pregnancies. Fetal rest-activity cycles coupled with arbitrary test intervals appear to lead to falsely nonreactive tests. Methods to alter fetal behavioral states have not been uniformly successful. A retrospective analysis of the adjunctive use of acoustic stimulation at our institution demonstrated a 50% reduction in the number of nonreactive tests. Consequently a prospective randomized clinical trial was undertaken to compare the standard nonstress test with the fetal acoustic stimulation test. Those patients randomized to the fetal acoustic stimulation test underwent transabdominal acoustic stimulation with a Model 5C electronic artificial larynx. The incidence of nonreactive tests was 14% in the control group and 9% in the study group (chi 2 = 11.09, p = 0.004). A significant reduction in testing time was also observed. The fetal acoustic stimulation test offers advantages over the traditional nonstress test by lowering the incidence of nonreactive tests and reducing testing time.", "The nonstress test (NST) is a helpful adjunct in the management of high-risk pregnancies. It has high predictability and a low false-negative rate but unfortunately has fairly high false-positive results. Attempts have been made to find a suitable stimulant to help decrease nonreactive results as well as to shorten the duration of testing: the recently introduced fetal acoustic stimulation test (AST) may have such attributes. This prospective, randomized clinical trial was carried out to assess the new test. A total of 1,300 individual tests were performed on high-risk pregnancies. Cases were randomized to receive either the AST or NST. All tracings were interpreted blindly by an independent perinatologist. The incidence of nonreactive tests was 6.8% in the AST group and 13.8% in the NST group (P < .001). There was a significant reduction in the time needed for a reactive test to occur. It can be concluded, therefore, that AST offers a greater advantage over NST by lowering both the incidence of nonreactive tests and testing time, thereby resulting in less of a need for the contraction stress test and biophysical profile.", "Two methods of vibroacoustic stimulation were compared with traditional nonstress tests. Fetal heart rate tracings following stimulation had more accelerations and were of greater amplitude and duration than in the control group. The length of time required to obtain a reactive nonstress test was almost 15 minutes shorter when vibroacoustic stimulation was applied than when vibroacoustic stimulation was not used. Vibroacoustic stimulation elicited a heightened reactivity that persisted beyond the observation period in 30 of 45 (67%) of the experimental group subjects.", "In this prospective blind study, 735 patients with high-risk pregnancies referred for antepartum testing of fetal well-being were randomly assigned to either a fetal biophysical profile scoring (375 patients) or a nonstress testing scheme (360 patients). Management was based on the results of antepartum tests, but the method of testing used was not disclosed. Fetal biophysical profile scoring resulted in a significantly higher positive predictive value in regards to low Apgar scores. Sensitivity, specificity, and accuracy, although higher with fetal biophysical profile scoring, did not demonstrate significant differences when compared with the nonstress test. The negative predictive value between the two methods was similar. All major anomalies were detected during ultrasound scanning, whereas none of these anomalies were detected by heart rate testing alone.", "To assess the effect on obstetric practice of clinician access to umbilical artery Doppler ultrasound results.\n Randomised controlled trial.\n A large teaching hospital.\n Two thousand two hundred and eighty-nine pregnancies defined as being at risk by referral for Doppler or fetal monitoring.\n Continuous wave Doppler studies of umbilical artery. Results immediately available to clinicians.\n Fetal outcome: perinatal mortality, Apgar score and admission to the neonatal unit. Obstetric intervention: admission to hospital, induction of labour and caesarean section. Use of of fetal well being: cardiotocography, biophysical profile and ultrasound biometry.\n The treatment and control groups were comparable in age, parity, gestation at point of entry and risk features. There were no overall differences in perinatal outcome, obstetric intervention or use of fetal monitoring. Examination of a subset recruited only because of hypertension or suspected intrauterine growth retardation (n = 754) similarly showed no difference attributable to group randomisation. Comparison of only those pregnancies retrospectively defined as low risk and high risk showed more use of cardiotocography in the high risk group with access to Doppler (P = 0.007) but no difference in the low risk group.\n Doppler umbilical artery recording has been shown to perform well in prediction power of antenatal fetal compromise. What has been examined in this study is the response of clinicians to the test. The results suggest that obstetricians do not use the test to modify their risk assessment, and, therefore, the need for fetal monitoring in particular pregnancies. There is a real need for accumulation of information from very large data sets, particularly in the prediction power of Doppler for antenatal fetal compromise from apparently chronic utero-placental cause to guide use of monitoring resources. If simply added to existing fetal monitoring techniques in a hospital where these are widely used, then umbilical artery Doppler recordings may at present simply involve extra resources of staff and expenses, without benefit.", "The ability of vibratory acoustic stimulation to shorten the duration of antepartum fetal heart rate monitoring was investigated by a randomized controlled trial. Vibratory acoustic stimulation did not shorten the overall duration of testing. This failure to improve the performance of antepartum monitoring appeared to result from prolonged accelerations, which complicated one third of the tests in which vibratory acoustic stimulation was employed. Further investigation is warranted using less profound methods of fetal stimulation." ]
"There are insufficient data from randomised trials to guide practice regarding the management of DFM. Based on the results of other systematic reviews of management strategies for women whose babies are thought to be at risk of compromise for various reasons, the following strategies show promise and may be prioritised for further research: Doppler ultrasound studies, computerised cardiotocography, and fetal arousal to facilitate cardiotocography. For settings where electronic fetal assessment methods are not available, clinical fetal arousal tests should be investigated."
"CD004667"
[ "8924098", "11251497", "2927328", "11251496", "7565233", "11212998", "12787235", "8494832", "11080465" ]
[ "A randomized, controlled trial of nurse-midwifery care.", "Team midwifery care in a tertiary level obstetric service: a randomized controlled trial.", "The 'Know Your Midwife' scheme--a randomised trial of continuity of care by a team of midwives.", "Does team midwife care increase satisfaction with antenatal, intrapartum, and postpartum care? A randomized controlled trial.", "Continuity of care by a midwife team versus routine care during pregnancy and birth: a randomised trial.", "Collaboration in maternity care: a randomised controlled trial comparing community-based continuity of care with standard hospital care.", "Changing Childbirth: a pilot project.", "Simulated home delivery in hospital: a randomised controlled trial.", "A randomised study of midwifery caseload care and traditional 'shared-care'." ]
[ "In 1990 a pilot nurse-midwifery program was implemented in a tertiary care hospital in a major western Canadian city. a randomized, controlled trial was conducted to determine if, when maternal and newborn patient outcomes were compared, the midwifery program was as effective as traditional, low-risk health care available in the city.\n All low-risk women who requested and qualified for nurse-midwifery care were randomly assigned to an experimental or control group.\n One hundred one women received care from nurse-midwives and 93 received standard care from either an obstetrician or family physician. The rate of cesarean delivery in the nurse-midwife group was 4 percent compared with 15.1 percent in the physician group. The episiotomy rate, excluding cesarean deliveries, for the nurse-midwife group was 15.5 percent compared with 32.9 percent in the physician group. The rates of epidural anesthesia for pain relief in labor were 12.9 percent and 23.7 percent, respectively. Statistically significant differences were found ultrasound examinations, amniotomy, intravenous drug administration during labor, dietary supplements, length of hospital stay, and admission of infants to the neonatal intensive care unit.\n The results clearly support the effectiveness of the pilot nurse-midwifery program and suggest that more extensive participation of midwives in the Canadian health care system is an appropriate use of health care dollars.", "In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through to the postpartum period was implemented for women attending Monash Medical Centre, a tertiary level obstetric service, in Melbourne, Australia. The objective of this study was to compare the new model of care with standard maternity care.\n In a randomized controlled trial, 1000 women who booked at the antenatal clinic and met the eligibility criteria were randomly allocated to receive continuity of midwifery care (team care) from a group of seven midwives in collaboration with obstetric staff, or care from a variety of midwives and obstetric staff (standard care). The primary outcome measures were procedures in labor, maternal outcomes, neonatal outcomes, and length of hospital stay.\n Women assigned to the team care group experienced less augmentation of labor, less electronic fetal monitoring, less use of narcotic and epidural analgesia, and fewer episiotomies but more unsutured tears. Team care women stayed in hospital 7 hours less than women in standard care. More babies of standard care mothers were admitted to the special care nurseries for more than 5 days because of preterm birth, and more babies of team care mothers were admitted to the nurseries for more than 5 days with intrauterine growth retardation. No differences occurred in perinatal mortality between the two groups.\n Continuity of midwifery care was associated with a reduction in medical procedures in labor and a shorter length of stay without compromising maternal and perinatal safety. Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service.", "A team of four midwives provided the majority of care during pregnancy, labour and the puerperium to 503 women at low obstetric risk, over a 2-year period. Compared with standard hospital care randomly allocated to 498 women this 'Know Your Midwife' scheme was associated with greater continuity in all phases of maternity care. The scheme appeared very acceptable to women: they spent less time in the antenatal clinic, and overall, felt more satisfied, better prepared and better able to discuss problems. The scheme was characterised by less obstetric intervention particularly in respect of augmentation of labour and intrapartum analgesia; labours tended to be longer. Neonatal outcome was generally similar in the two groups but the size of the trial did not allow a precise assessment of differential effects in these terms. The 'Know Your Midwife' scheme is feasible. It should now be introduced more widely but in a way which allows continuing evaluation.", "Although policymakers have suggested that improving continuity of midwifery can increase women's satisfaction with care in childbirth, evidence based on randomized controlled trials is lacking. New models of care, such as birth centers and team midwife care, try to increase the continuity of care and caregiver. The objective of this study was to evaluate the effect of a new team midwife care program in the standard clinic and hospital environment on satisfaction with antenatal, intrapartum, and postpartum care in low-risk women in early pregnancy.\n Women at Royal Women's Hospital in Melbourne, Australia, were randomly allocated to team midwife care (n = 495) or standard care (n = 505) at booking in early pregnancy. Doctors attended most women in standard care, and continuity of the caregiver was lacking. Satisfaction was measured by means of a postal questionnaire 2 months after the birth.\n Team midwife care was associated with increased satisfaction, and the differences between the groups were most noticeable for antenatal care, less noticeable for intrapartum care, and least noticeable for postpartum care. The study found no differences between team midwife care and standard care in medical interventions or in women's emotional well-being 2 months after the birth.\n Conclusions about which components of team midwife care were most important to increased satisfaction with antenatal care were difficult to draw, but data suggest that satisfaction with intrapartum care was related to continuity of the caregiver.", "To compare continuity of care from a midwife team with routine care from a variety of doctors and midwives.\n A stratified, randomised controlled trial.\n 814 women attending the antenatal clinic of a tertiary referral, university hospital.\n Women were randomly allocated to team care from a team of six midwives, or routine care from a variety of doctors and midwives.\n Antenatal, intrapartum and neonatal events; maternal satisfaction; and cost of treatment.\n 405 women were randomly allocated to team care and 409 to routine care; they delivered 385 and 386 babies, respectively. Team care women were more likely to attend antenatal classes (OR, 1.73; 95% CI, 1.23-2.42); less likely to use pethidine during labour (OR, 0.32; 95% CI, 0.22-0.46); and more likely to labour and deliver without intervention (OR, 1.73; 95% CI, 1.28-2.34). Babies of team care mothers received less neonatal resuscitation (OR, 0.59; 95% CI, 0.41-0.86), although there was no difference in Apgar scores at five minutes (OR, 0.86; 95% CI, 0.29-2.57). The stillbirth and neonatal death rate was the same for both groups of mothers with a singleton pregnancy (three deaths), but there were three deaths (birthweights of 600 g, 660 g, 1340 g) in twin pregnancies in the group receiving team care. Team care was rated better than routine care for all measures of maternal satisfaction. Team care meant a cost reduction of 4.5%.\n Continuity of care provided by a small team of midwives resulted in a more satisfying birth experience at less cost than routine care and fewer adverse maternal and neonatal outcomes. Although a much larger study would be required to provide adequate power to detect rare outcomes, our study found that continuity of care by a midwife team was as safe as routine care.", "To test whether a new community-based model of continuity of care provided by midwives and obstetricians improved maternal clinical outcomes, in particular a reduced caesarean section rate.\n Randomised controlled trial.\n A public teaching hospital in metropolitan Sydney, Australia. Sample 1089 women randomised to either the community-based model (n = 550) or standard hospital-based care (n = 539) prior to their first antenatal booking visit at an Australian metropolitan public hospital.\n Data were collected on onset and outcomes of labour, antenatal, intrapartum and postnatal complications, antenatal admissions to hospital and neonatal mortality and morbidity.\n There was a significant difference in the caesarean section rate between the groups, 13.3% (73/550) in the community-based group and 17.8% in the control group (96/539). This difference was maintained after controlling for known contributing factors to caesarean section (OR = 0.6, 95% CI 0.4-0.9, P = 0.02). There were no other significant differences in the events during labour and birth. Eighty babies (14.5%) from the community-based group and 102 (18.9%) from the control group were admitted to the special care nursery, but this difference was not significant (OR 0.75, 95% CI 0.5-1.1, P = 0.12). Eight infants died during the perinatal period (four from each group), for an overall perinatal mortality rate of 7.3 per 1000 births.\n Community-based continuity of maternity care provided by midwives and obstetricians resulted in a significantly reduced caesarean section rate. There were no other differences in clinical outcomes.", "To compare the outcomes of an adapted pilot Changing Childbirth initiative providing continuity of care by a group of known midwives with traditional maternity care.\n Between-groups trial to compare levels of satisfaction and clinical outcomes for two groups of women, cared for either under this Changing Childbirth scheme or the traditional model of care.\n Of the 200 women who agreed to participate in the project, 100 were randomly allocated to the pilot scheme and 100 to the traditional care package. During the postpartum period, information was collected via a questionnaire about participants' levels of satisfaction with a variety of aspects of care provided during the antenatal, delivery and postpartum periods. Data about clinical outcomes for the two groups were also obtained.\n Women in the pilot group had significantly more continuity of care throughout each of the three periods, were generally more satisfied with their care, felt that they had more choice over a variety of aspects of care and experienced no compromise in clinical outcomes (P = 0.05 or less in each case).\n Many previous attempts to introduce the Changing Childbirth initiative have revealed significant problems, particularly with regard to the continuity of carer requirement. Taking account of local health care needs and existing provision, the present study adapted this concept to continuity of care. This did not apparently affect any of the guiding principles contained in the original document, and yet enhanced satisfaction. It would appear that the Changing Childbirth agenda can be adapted and integrated with local health care situations without sacrificing any of the overarching principles.", "To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife-led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant-led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out.\n Randomised controlled trial.\n Leicester Royal Infirmary Maternity Hospital.\n Of 3510 women who were randomised, 2304 were assigned to the midwife-led scheme and 1206 were assigned to the consultant-led scheme.\n Complications in the antenatal, intrapartum and postpartum periods were compared as was maternal morbidity and fetal mortality and morbidity. Satisfaction of the women with care over different periods of the pregnancy and birth were assessed.\n There were few significant differences in antepartum, intrapartum and postpartum events between the two groups. There was no difference in the percentage of mothers and babies discharged home alive and well. Generally higher levels of satisfaction with care antenatally and during labour and delivery were shown in those women allocated to midwife care.", "To evaluate caseload midwifery care in comparison to traditional 'shared care'.\n Comparative study with area randomisation.\n District general hospital in England.\n 'Known carer at delivery,' 'normal vaginal delivery' and 'obstetric intervention'.\n All pregnant women delivering in the six areas chosen for the study.\n A highly significant difference was found between caseload and traditional care groups in terms of level of 'known carer at delivery' (696/770 94.7%; cf. 52/735 (6.7%), p < 0.001). However, no differences in 'normal vaginal delivery' rates were found (542/770 (70%) cf. 509/735 (69%). There were fewer 'obstetric interventions' in the caseload group, particularly epidural analgesia (80/770 (10%) cf. 110/735 (15%) p = 0.01) and oxytocin augmentation (351/77 (46%) cf. 387/735 (53%), p = 0.01). There were no significant differences found in terms of neonatal outcome.\n Caseload midwifery results in high levels of 'known carer at delivery' which appears to be associated with a reduction in augmentation and epidural rates but which were not associated with an increase in normal vaginal delivery rate." ]
"Most women should be offered midwife-led models of care and women should be encouraged to ask for this option although caution should be exercised in applying this advice to women with substantial medical or obstetric complications."
"CD006164"
[ "15230999", "10701059", "7835254" ]
[ "School-milk intervention trial enhances growth and bone mineral accretion in Chinese girls aged 10-12 years in Beijing.", "[Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3].", "Factors affecting the morbidity of vitamin D deficiency rickets and primary protection." ]
[ "A 2-year milk intervention trial was carried out with 757 girls, aged 10 years, from nine primary schools in Beijing (April 1999 - March 2001). Schools were randomised into three groups: group 1, 238 girls consumed a carton of 330 ml milk fortified with Ca on school days over the study period; group 2, 260 girls received the same quantity of milk additionally fortified with 5 or 8 microg cholecalciferol; group 3, 259 control girls. Anthropometric and bone mineralisation measurements, as well as dietary, health and physical-activity data, were collected at baseline and after 12 and 24 months of the trial. Over the 2-year period the consumption of this milk, with or without added cholecalciferol, led to significant increases in the changes in height (> or =0.6 %), sitting height (> or =0.8 %), body weight (> or 2.9 %), and (size-adjusted) total-body bone mineral content (> or =1.2 %) and bone mineral density (> or =3.2 %). Those subjects receiving additional cholecalciferol compared with those receiving the milk without added 25-hydoxycholecalciferol had significantly greater increases in the change in (size-adjusted) total-body bone mineral content (2.4 v. 1.2 %) and bone mineral density (5.5 v. 3.2 %). The milk fortified with cholecalciferol significantly improved vitamin D status at the end of the trial compared with the milk alone or control groups. It is concluded that an increase in milk consumption, e.g. by means of school milk programmes, would improve bone growth during adolescence, particularly when Ca intake and vitamin D status are low.", "Recent studies have shown a high prevalence of calcium and vitamin D deficiencies in adolescents. The aim of this present study was to follow the changes in calcium status and 25 hydroxyvitamin D (25[OH]D) and parathyroid hormone (iPTH) levels during winter in preadolescents and adolescents from four university hospitals in northern France.\n Two groups of teenagers and adolescents (range: 10-15 years) were followed from October 1996 to June 1997. They were given either 100,000 IU of vitamin D (treated group n = 33) or a placebo (control group n = 35) in October, January and April. Serum calcium, phosphate, 25(OH)D and iPTH levels were measured at inclusion and every three months thereafter.\n At inclusion, plasma or serum 25(OH)D levels were < or = 10 ng/mL in 16 subjects and < 6 ng/mL in six. In control children, no significant change in 25(OH)D occurred during the study, while plasma or serum iPTH levels increased to 34 +/- 11 pg/mL. In the treated groups, 25(OH)D levels remained > 20 ng/mL in every subject; no hypercalcemia was observed; and the mean plasma or serum iPTH level was 25 +/- 14 pg/mL at the end of the study.\n Teenagers presented with a high prevalence of biological vitamin D deficiency at the end of summer. The increase of iPTH during winter in the unsupplemented group suggests that this has secondary consequences on their calcium homeostasis unless they are supplemented with vitamin D. We advocate a sufficient calcium supply and a 100,000 IU vitamin D supplement given two or three times during winter to preadolescents and adolescents living in northern France.", "Rickets was investigated in 860 children in the 3 to 36 month age group in 21 villages attached to Sinik Health Centre, in northeastern Turkey. The blood calcium, phosphorus and alkaline phosphatase levels of suspect cases were determined following examination and wrist x-rays taken. The prevalence of cross-sectional rickets was determined, in the cohort group formed by removing the rickets cases (to the first group, advice was not given; to the second, 400 IU of vitamin D) and its incidence determined. The prevalence of rickets was calculated as 9.8% with no distinction observed between males and females (P > 0.05). It is higher in children in the 3-6 month group (23.97%) (P < 0.05); exposed rarely to the sun (P < 0.001); without fish in diet (P < 0.01); born to mother under 18 years old (P < 0.001); with a mother not using contraception (P < 0.01). The prevalence of acute respiratory infections (ARI) was calculated as 47.62% and 35.70% (P < 0.05) in children with and without rickets, respectively. The prevalence of enteritis was calculated as 29.76% and 18.43% (P < 0.05) in children with rickets and without rickets, respectively. Rickets was not seen where 400 IU of vitamin D was administered, while incidence for the twelve-month period was calculated as 3.8% in the other group. Combatting rickets is important in developing countries where deaths under five years are largely due to ARI and enteritis." ]
"There a only few studies on the prevention of nutritional rickets in term born children. Until new data become available, it appears sound to offer preventive measures (vitamin D or calcium) to groups of high risk, like infants and toddlers; children living in Africa, Asia or the Middle East or migrated children from these regions into areas where rickets is not frequent. Due to a marked clinical heterogeneity and the scarcity of data, the main and adverse effects of preventive measures against nutritional rickets should be investigated in different countries, different age groups and in children of different ethnic origin."
"CD003996"
[ "9432077", "7282909", "3172958", "4997484", "3402097", "3530224", "9738752", "3124628", "11773839", "7810316" ]
[ "Use of antibiotic prophylaxis in ear surgery.", "Effectiveness of prophylactic antibiotic treatment in mastoid surgery.", "Antimicrobial prophylaxis in ear surgery.", "Prophylactic antibiotics in otolaryngologic surgery: a double-blind study.", "Tympanoplasty surgery and prophylactic antibiotics: surgical results.", "Efficacy of perioperative ceftazidime in the surgical treatment of chronic otitis media due to Pseudomonas aeruginosa. Preliminary report of a prospective, controlled study.", "Prophylactic antibiotics in surgery for chronic ear disease.", "The role of prophylactic antibiotics in middle ear surgery. A study on phenoxymethylpenicillin prophylaxis.", "Preoperative topical ofloxacin solution for tympanoplasty: a randomized, controlled study.", "[Antibiotic prophylaxis in otological and otoneurological surgery]." ]
[ "A prospective, double-blind, randomized, placebo-controlled study was performed to evaluate the effect of antibiotic prophylaxis in ear surgery. The present study reports on the results of 750 patients, half of whom received cefuroxime for 1 day, the other half, placebo. All postoperative infections occurring within 2 weeks after the intervention were recorded, together with several preoperative and perioperative parameters. It is concluded that exploratory tympanoplasties (including stapedotomy) and \"dry perforation\" tympanoplasties should be considered \"clean\" operations according to the American National Research Council and do not benefit from antibiotic prophylaxis. On the other hand, tympanoplasties performed on draining ears and on ears with cholesteatoma should be considered \"dirty\" operations for which antibiotic prophylaxis may decrease the postoperative infection rate by factor 3. All postoperative infections healed without sequels under proper treatment, except for three that resulted in graft necrosis--one in the placebo group and two in the cefuroxime group. In consequence, prophylaxis may not be mandatory in the dirty group, although the authors advocate its use for the sake of patient and surgeon comfort.", "This article describes a prospective study of the effectiveness of prophylactic antibiotic treatment in preventing infection following mastoid surgery. Seventy-two patients who underwent surgery for chronic middle ear disease served as the basis for this study. Bacteriologic findings from middle ear discharge, showing aerobic and anaerobic bacteria, are reported. The patients were randomly classified into two groups, one undergoing surgery with preventive antibiotic treatment with clindamycin and gentamycin and the other undergoing surgery without antibiotic therapy. The early postoperative inflammatory complications are presented. No significant differences were found in the incidence of these complications between the two groups. In view of the results, the effectiveness of preventive antibiotic treatment in mastoid surgery is questioned.", "The purpose of this research was to assess the efficacy of prophylactic antibiotic administration in ear surgery over a wide range of cases. Additional objectives include the assessment of the relative effect of patient age, duration of operation, preoperative condition, and the success of tympanoplasty. Prospectively, in a controlled study, 4,000 patients were studied employing cephalosporin and oxacillin as prophylactic antimicrobials. No statistically significant difference in postoperative otologic infection rates was observed. This conclusion was unaltered by the operative duration, patient age, or preoperative condition. Grafting success was not improved.", "nan", "This paper reports a multicentre, controlled, blind, prospective, randomized study into the use of prophylactic systemic antibiotics in myringoplasty surgery. A total of 130 individuals were randomly allocated to either an antibiotic or a non-antibiotic group. Each individual was clinically and audiometrically assessed preoperatively, and 8 weeks postoperatively. It was found that systemic prophylactic antibiotics did not influence either the success rate of myringoplasty surgery or the audiometric result.", "A prospective open and controlled study of perioperative antibiotics was conducted in patients with chronic otitis media (COM). Drug efficacy was found in a subgroup of 26 patients, who were characterized by preoperative aural drainage culturing Pseudomonas aeruginosa. Fourteen of these patients were randomized to receive ceftazidime (cephalosporin) for 5 days at the operation, while 12 had no antibiotic treatment. The occurrence of subsequent aural drainage was compared with the actual clinical and microbiological conditions of the ears 2 months after the operation; statistically significant differences were found in favor of the group treated with ceftazidime. Further studies must define the role of ceftazidime and other antibiotics in the management of patients with COM.", "The role of prophylactic antibiotics in otologic surgery continues to be debated and perhaps misused. Prior studies have provided conflicting evidence with regard to the benefit obtained from the use of prophylactic antibiotics in surgery for chronic otitis media. The current study was designed to evaluate the role of prophylactic antibiotics in the outcomes of surgery for chronic ear disease. It was the authors' impression that there was no indication for prophylactic antibiotics in such surgery.\n Randomized prospective study performed in a tertiary care facility.\n Patients who met inclusion criteria (n = 146) were randomly assigned to an antibiotic treatment group or a control group receiving no prophylactic antibiotics. Patients in the antibiotic treatment group were given preoperative intravenous antibiotics followed by oral antibiotics for 5 days after surgery. Patients were followed postoperatively and observed for clinical evidence of infection and graft failure.\n There was no statistically significant difference between the two groups with regard to the incidence of postoperative infection or graft survival.\n The use of prophylactic antibiotics in surgery for chronic ear disease cannot be recommended based on the findings of this study.", "A randomized prospective double-blind study was performed testing the value of phenoxymethylpenicillin in conjunction with middle ear surgery. The patients were evaluated for clinical signs of infection and with bacteriologic cultures both pre- and postoperatively. No difference in clinical signs of infection was noted between the pre- and postoperative evaluations. A significantly larger number of patients, however, presented with postoperative positive bacteriologic cultures as compared with the preoperative cultures. This increase was particularly evident in the placebo group. The two microorganisms that were found in increased numbers postoperatively were Staphylococcus epidermidis and Pseudomonas strains. The value of prophylactic antibiotic treatment and phenoxymethylpenicillin treatment in particular is discussed.", "To establish the efficacy of immediate preoperative ototopical ofloxacin eardrops in eradicating middle ear pathogens and improving operative outcome.\n Single-blind, randomized control study.\n Tertiary referral center, ambulatory clinic, and hospital setting.\n Consecutive patients with chronic suppurative otitis media for Type I tympanoplasty (myringoplasty).\n The patients were randomly assigned to 3 groups: Group A underwent 10-minute daily treatments with eardrops for 2 weeks before surgery, Group B underwent 3-minute daily treatments for 2 weeks before surgery, and Group C underwent no treatment.\n Preoperative and perioperative bacteriology and success of the surgery as defined by an intact tympanic membrane in the eighth week postsurgery.\n There were 101 patients entered in the study. The preoperative, perioperative, and postoperative observation of discharge and quantity of the discharge were compared, and no differences were found among the groups (Kruskal-Wallis test). The perioperative culture results were analyzed and 18/21 (86%) became culture negative in Group A, 23/27 (85%) became culture negative in Group B, and 3/21 (14%) became culture negative in the control group (Group C versus Group A or Group B, chi(2) tests p < 0.001). The success rates of surgery as defined by an intact tympanic membrane showed no difference: 28/33 (85%), 27/33 (82%), and 31/35 (89%) in Groups A, B, and C, respectively. The preoperative positive bacteriology rate in the surgical failures was 10/15 (67%), compared with 16/76 (21%) for the successful procedures (p < 0.001).\n Our study has shown that ofloxacin successfully eradicates most bacterial flora preoperatively. We cannot, however, confirm the benefits of its preoperative usage in improving the graft success rate.", "nan" ]
"There is no strong evidence that the large-scale use of prophylactic antibiotics in clean and clean-contaminated ear surgery is helpful in reducing postoperative complications such as wound infection, discharge from the outer ear canal, labyrinthitis and graft failure."
"CD005146"
[ "17954515", "14512476", "17954514" ]
[ "Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine.", "Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine.", "Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine." ]
[ "To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine.\n Pragmatic randomised open trial (January-July 2004).\n Psychiatric emergency room, Rio de Janeiro, Brazil.\n 316 patients who needed urgent intramuscular sedation because of agitation, dangerous behaviour, or both.\n Open treatment with intramuscular haloperidol 5-10 mg or intramuscular haloperidol 5-10 mg plus intramuscular promethazine up to 50 mg; doses were at the discretion of the prescribing clinician.\n The primary outcome was proportion tranquil or asleep by 20 minutes. Secondary outcomes were asleep by 20 minutes; tranquil or asleep by 40, 60, and 120 minutes; physically restrained or given additional drugs within 2 hours; severe adverse events; another episode of agitation or aggression; additional visit from the doctor during the subsequent 24 hours; overall antipsychotic load in the first 24 hours; and still in hospital after 2 weeks.\n Primary outcome data were available for 311 (98.4%) people, 77% of whom were thought to have a psychotic illness. Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone (relative risk 1.30, 95% confidence interval 1.10 to 1.55; number needed to treat 6, 95% confidence interval 4 to 16; P=0.002). No differences were found after 20 minutes. However, 10 cases of acute dystonia occurred, all in the haloperidol alone group.\n Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety. Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects.\n Current Controlled Trials ISRCTN83261243 [controlled-trials.com].", "To compare two widely used drug treatments for people with aggression or agitation due to mental illness.\n Pragmatic, randomised clinical trial.\n Three psychiatric emergency rooms in Rio de Janeiro, Brazil.\n 301 aggressive or agitated people.\n Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine.\n Patients tranquil or sedated at 20 minutes. Secondary outcomes: patients tranquil or asleep by 40, 60, and 120 minutes; restrained or given extra drugs within 2 hours; severe adverse events; another episode of agitation or aggression; needing extra visits from doctor during first 24 hours; overall antipsychotic load in first 24 hours; and not discharged by two weeks.\n 151 patients were randomised to midazolam, and 150 to haloperidol-promethazine mix. Follow up for the primary outcome was available for 298 (99%): 134/151 (89%) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 (67%) of those given haloperidol plus promethazine (relative risk 1.32 (95% confidence interval 1.16 to 1.49)). By 40 minutes, midazolam still had a statistically and clinically significant 13% relative advantage (1.13 (1.01 to 1.26)). After 1 hour, about 90% of both groups were tranquil or asleep. One important adverse event occurred in each group: a patient given midazolam had transient respiratory depression, and one given haloperidol-promethazine had a grande mal seizure.\n Both treatments were effective. Midazolam was more rapidly sedating than haloperidol-promethazine, reducing the time people are exposed to aggression. Adverse effects and resources to deal with them should be considered in the choice of the treatment.", "To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness.\n Pragmatic, allocation concealed, randomised controlled trial.\n Emergency services of a general hospital psychiatry department in Vellore, south India.\n 300 adults with agitated or violent behaviour as a result of mental illness; 150 randomised to intramuscular olanzapine and 150 randomised to intramuscular haloperidol plus promethazine.\n Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine.\n Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes. Secondary outcomes were proportion of patients who were tranquil, asleep, restrained, absconding, or clinically improved at 15, 30, 60, 120, and 240 minutes; additional medical interventions and adverse effects over four hours; and compliance with oral drugs and adverse effects over two weeks.\n Of 300 people randomised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine, follow-up data were available for primary outcomes for 298 (99%). Both treatments resulted in similar proportions of people being tranquil or asleep at 15 minutes (olanzapine 131/150 (87%), haloperidol plus promethazine 136/150 (91%); relative risk 0.96, 95% confidence interval 0.34 to 1.47) and 240 minutes (olanzapine 144/150 (96%), haloperidol plus promethazine 145/150 (97%); relative risk 0.99, 0.95 to 1.03). However, more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours (65/150 (43%) v 31/150 (21%); relative risk 2.07, 1.43 to 2.97). Adverse effects were uncommon with both treatments.\n Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination resulted in fewer additional medical interventions within four hours of intervention.\n Clinical trials NCT00455234 [ClinicalTrials.gov]." ]
"All treatments evaluated within the included studies are effective. Benzodiazepines, however, have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and use of this group of drugs outside of services fully confident of observing for and managing the consequences of respiratory distress is difficult to justify. Haloperidol used on its own is at such risk of generating preventable adverse effects that unless it is the only choice, this evidence directs that this sole treatment should be avoided. Olanzapine IM is valuable when compared with haloperidol plus promethazine but its duration of action is short and re-injection is frequently needed. Haloperidol plus promethazine used in two diverse situations in Brazil and India has much evidence to support its swift and safe clinically valuable effects."
"CD001744"
[ "1586049", "9337824", "15316206", "10596681" ]
[ "A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.", "Effect of long-term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia.", "Long-term oxygen therapy stops the natural decline of endurance in COPD patients with reversible hypercapnia.", "A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients." ]
[ "The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "To date only two controlled studies have been published on the effects of domiciliary oxygen treatment on survival in patients with chronic obstructive pulmonary disease (COPD) with advanced respiratory failure. The survival in such patients despite oxygen treatment remains poor. The prescription of long term oxygen therapy (LTOT) in less severe disease remains controversial. The aim of this study was to evaluate the rationale for prescribing oxygen to patients with COPD with moderate hypoxaemia.\n One hundred and thirty five patients with COPD, with PaO2 7.4-8.7 kPa (56-65 mmHg) and advanced airflow limitation (mean (SD) forced expiratory volume in one second (FEV1) 0.83 (0.28) 1), were randomly allocated to a control (n = 67) and LTOT (n = 68) group. The patients were followed every three months for at least three years or until death.\n The cumulative survival rate was 88% at one year, 77% at two years, and 66% at three years. No significant differences were found in survival rates between patients treated with LTOT and controls, nor did longer oxygen use (over 15 hours per day) improve survival. Younger age, better spirometric values, and higher body mass index predicted better survival.\n Domiciliary oxygen treatment does not prolong survival in patients with COPD with moderate hypoxaemia. Airway limitation seems to determine survival in this group of patients.", "Respiratory muscle weakness is one of the most important causes of hypercapnia in patients with COPD. There is evidence that stable hypercapnic patients will benefit from long-term oxygen therapy (LTOT).\n The prognostic role of reversible hypercapnia in COPD is still unclear. Early implementation of LTOT in these patients may influence endurance time and mortality.\n In this pilot study, we investigated 28 patients (26 males, 49-74 years) with COPD, advanced airflow limitation [forced expiratory volume in 1 s (percentage of predicted value) 40.8 +/- 10.2] and mild hypoxaemia (pO(2) 66.5 +/- 6.3 mm Hg). All patients had developed a moderate reversible hypercapnia during an acute exacerbation or during exercise testing (peak pCO(2) 48.0 +/- 2.5 mm Hg). Patients were allocated randomly to a control group (n = 14) or an LTOT group (n = 14). The two groups were well matched in terms of physiological data. Lung function, endurance time (cycle ergometer), dyspnoea score, blood gases and LTOT compliance were measured at baseline and every 6 months over a period of 3 years.\n Endurance time increased from 6.4 +/- 2.7 min at baseline to 7.1 +/- 2.7 min after 1 year in the LTOT group and decreased from 6.1 +/- 3.0 to 4.9 +/- 3.8 min in the controls (p < 0.05). After 1 year, the end-exercise dyspnoea score was significantly lower in the LTOT group (4.5 +/- 1.5) than in the controls (5.7 +/- 1.9).\n COPD patients with reversible hypercapnia and mild hypoxaemia benefit from LTOT in terms of endurance time and a reduction of exertional dyspnoea after 1 year.\n Copyright 2004 S. Karger AG, Basel", "The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients." ]
"Long-term home oxygen therapy improved survival in a selected group of COPD patients with severe hypoxaemia (arterial PaO2 less than 55 mm Hg (8.0 kPa)). Home oxygen therapy did not appear to improve survival in patients with mild to moderate hypoxaemia or in those with only arterial desaturation at night."
"CD004931"
[ "2792672", "15672051", "3294079", "2194894", "2767500", "3294080" ]
[ "A double-blind, randomized, sham-controlled trial of the gastric bubble for obesity.", "Intragastric balloon for treatment-resistant obesity: safety, tolerance, and efficacy of 1-year balloon treatment followed by a 1-year balloon-free follow-up.", "Double-blind controlled trial of the Garren-Edwards gastric bubble: an adjunctive treatment for exogenous obesity.", "Intragastric balloon in the treatment of super-morbid obesity. Double-blind, sham-controlled, crossover evaluation of 500-milliliter balloon.", "Effect of the gastric balloon versus sham procedure on weight loss in obese subjects.", "Effect of gastric bubble as a weight reduction device: a controlled, crossover study." ]
[ "We investigated the effect of an endoscopically placed gastric balloon, the Garren-Edwards gastric bubble (GEGB), on weight loss in obese patients. Fifty-nine obese patients were entered into a prospective double-blind study and randomized into two groups. In one group (34 patients) the GEGB was inserted, and in the other group (25 patients) a sham insertion was done. All patients participated in a standard weight loss program consisting of dietary therapy, behavior modification, and physical exercise. The bubble was removed endoscopically after 3 months from both groups. Patients were followed for an additional 9 months after bubble removal and weight loss was monitored. Weight loss was the same in both groups at 3 months (18.7 lb vs. 17.2 lb). This was true whether determined by change in pounds, percentage of body weight, or body mass index. We concluded that the GEGB was of no added benefit as compared with sham insertion, when combined with a standard weight loss program. Because of the lack of proven efficacy and the relatively high cost, we recommend that such devices be restricted to controlled studies until significant benefits are proven.", "Prior efforts to treat obesity with intragastric balloons were thwarted by high complication rates. Therefore, fundamental requirements for optimal balloon designs were defined. The aim of the present study was to investigate the effectiveness, the safety, and the tolerance of a new intragastric balloon.\n Adults with treatment-resistant obesity and no GI contraindications to balloon placement were invited to participate in a randomized, double-blind trial of balloon or sham treatment of 3 months' duration. Patients (sham- and balloon-treated groups) in whom a preset weight-loss goal was achieved were given an additional 9 months of balloon treatment. After removal of the balloon at year 1, patients were followed for a second year without the balloon.\n Forty-three treatment-resistant patients (mean body mass index 43.3 kg/m 2) were enrolled. Five patients did not meet the preset weight-loss goal (nonresponse 11.6%). Three patients did not tolerate the balloon (7.0%), with endoscopy demonstrating severe esophagitis. Three other patients developed esophagitis that was related to use of nonsteroidal anti-inflammatory drugs, albeit prohibited (2 patients), or substantial weight loss with balloon treatment (1). In intention-to-treat analysis, sham- and balloon-treated groups had a similar mean weight loss of 11.2 kg (9.0%) and 12.9 kg (10.4%), respectively, during the first 3 months. During months 3 to 6, patients who had sham therapy in months 0 to 3 lost 8.8 kg (7.9%) during the first 3 months of balloon treatment. In contrast, patients in the balloon-treatment group lost 3.9 kg (3.5%) during months 3 to 6 (their second balloon treatment period). The overall weight loss was 20 kg (16.1%) and 16.7 kg (13.4%) after 6 months in the sham/balloon and in the balloon/balloon treated groups (not significant), respectively. After 1-year of balloon treatment, a mean weight loss of 21.3 kg (17.1%) was achieved in all patients, of which 12.6 kg (9.9%) was maintained at the end of the second balloon-free year; 47% of patients sustained a greater than 10% weight loss, with considerably reduced comorbidity. In 33 patients who completed the study per protocol, weight loss was 25.6 kg (20.5%) after 1 year and 14.6 kg (11.4%) after 2 years; 55% maintained a weight loss of greater than 10%. Interventional complications occurred in 1.6% (2/128) and balloon deflations in 2.3% (3/128).\n For patients with treatment-resistant obesity, the intragastric balloon appeared to be safe but was not a treatment option in a fifth of patients. Although an independent benefit of balloon treatment beyond diet, exercise, and behavioral therapy could not be demonstrated in the first 3 months, balloon treatment for 1 year resulted in substantial weight loss, the greater part of which was maintained during the balloon-free second year.", "Since its approval by the Food and Drug Administration in September 1985, the Garren-Edwards gastric bubble has been extensively used as an adjunct to diet and behavioral modification in the treatment of exogenous obesity. In an attempt to evaluate the efficacy of the Garren-Edwards gastric bubble, a double-blind crossover study was undertaken. Ninety patients were randomized into three groups: bubble-sham, sham-bubble, and bubble-bubble in two successive 12-wk periods. Sixty-one patients completed the entire 24-wk study. All groups participated in ongoing diet and behavioral modification therapy in a free-standing obesity program, the members of which were blinded to randomization arms. All patient groups lost weight during this study. The mean cumulative weight loss in pounds at 12 wk was as follows: bubble-sham = 19, sham-bubble = 12, and bubble-bubble = 8; and at 24 wk: bubble-sham = 23, sham-bubble = 16, and bubble-bubble = 18. The mean cumulative change in body mass index (kg/m2) at 12 wk was as follows: bubble-sham = -3.1, sham-bubble = -2.3, and bubble-bubble = -2.9; and at 24 wk: bubble-sham = -3.1, sham-bubble = -3.0, and bubble-bubble = -3.3. Although weight loss occurred more consistently in patients with a Garren-Edwards gastric bubble, there were no significant differences between any of the three groups at 12 or 24 wk with respect to weight loss or change in body mass index. The major part of the weight loss noted during this study occurred during the first 12-wk period, irrespective of therapy (bubble or sham). Side effects observed during this study included gastric erosions (26%), gastric ulcers (14%), small bowel obstruction (2%), Mallory-Weiss tears (11%), and esophageal laceration (1%). We conclude that, in this study, the use of a Garren-Edwards gastric bubble did not result in significantly more weight loss than diet and behavioral modification alone in the management of exogenous obesity, and it may result in significant morbidity.", "A prolonged randomized, prospective, double-blind, crossover study, including a sham-sham-treated group, was undertaken to evaluate the efficacy and safety of a 500-mL gastric bubble (Ballobes; DOT ApS, Rödovre, Denmark) as an adjunct to diet, physical training, and behavioral modification. Only supermorbidly obese patients who fulfilled the usual criteria for surgery were admitted. A weight loss of 38 kg in the first 17 weeks and another 12 kg in the second 18 weeks could be achieved. The body mass index, the percentage of overweight and the loss in percentage of initial weight, paralleled this impressive weight loss. In the second period, a plateau effect occurred after the massive changes in the first period, and only one third of the changes in all parameters was seen. Stratification into a sham-sham, sham-balloon, balloon-sham, and balloon-balloon group did not show any statistical difference for all parameters between the four groups. The double-blind nature of the study was affirmed by the patient's correct judgment of the presence or absence of a balloon in only 21% of the balloon and 44% of the sham procedures. Gastrointestinal complications were infrequent and consisted of erosions (three patients), asymptomatic reflux oesophagitis (one patient), and asymptomatic gastric ulcer (one patient). Only the latter patient had elevated gastrin levels. One patient could not tolerate the balloon. All balloons remained airtight during both parts of the study for a mean of 123 days. This study confirmed the safety of the balloon, but no additional benefit could be ascribed to the balloon compared with a very low-calorie diet and medical and dietary support.", "The mechanism by which intragastric balloons induce weight loss is not known, although they may act simply by reducing the amount of food needed to induce satiety. The knowledge that a balloon is present may influence the patients' eating patterns and reduce caloric intake and weight. In order to test whether the balloon or the secondary psychological effect caused weight loss, a double blind balloon versus sham procedure was devised with both groups receiving identical outpatient dietary advice (800 kcal/day). Twenty four obese women with body mass index greater than 30 kg/m2 from an obesity clinic were studied. Twelve had the balloon and 12 the sham procedure. The balloon was removed after three months and the patients were followed for a further three months. There was significantly greater weight loss in the balloon group, mean weight loss (SD) of 7.33 (6.12) kg compared with the sham group, mean weight loss (SD) of 3.33 (3.9) kg (p less than 0.05). Weight loss was not maintained in all patients after balloon removal. Side effects were more common in the balloon group (abdominal pain, nausea, and vomiting) but resolved by the second week. We conclude that the intragastric balloon is a safe and effective method of inducing weight loss in well motivated obese patients.", "In spite of the widespread use of the Garren-Edwards gastric bubble as an adjuvant device in weight reduction, its efficacy has not been established. Therefore, our purpose was to conduct a randomized, double-blind, crossover study of this device in the management of exogenous obesity. The study group consisted of 23 patients, 21 women and 2 men, ranging in age from 21 to 53 yr. Patients were 25%-111% above their ideal body weight. They were studied for 24 wk, consisting of two separate 12-wk evaluation periods. Patients were randomly assigned either to receive the gastric bubble or to have a sham procedure. After the first 12-wk evaluation period, the gastric bubble and sham were administered in crossover fashion, so that those who had received the gastric bubble initially received the sham later and vice versa. The study coordinator remained blind to the kind of treatment, weighed each patient biweekly, enforced dietary counseling, and provided behavior modification. Those who had passed or were found to have a deflated bubble at the end of the treatment period were excluded from the study. Mean weight reduction in the two evaluation periods did not differ significantly. Patients lost 5.4 +/- 1.7 kg (mean +/- SE) during the gastric bubble period and 5.20 +/- 0.8 kg during the sham period. The order of administration of the gastric bubble and sham did not significantly affect the result. The time-course of mean biweekly values, however, revealed that with the gastric bubble, weight loss was significantly greater only during first (p less than 0.005) and second (p less than 0.025) 2-wk evaluation periods. This difference, however, disappeared after the initial 4 wk of treatment. These observations suggest that although gastric bubble implantation reduced weight significantly more than the sham procedure initially, the mean weight loss during 12 wk of evaluation was not different between the two periods. In our opinion, the gastric bubble is of no value as an adjuvant device in weight reduction." ]
"Evidence from this review is limited for decision making, since there was large heterogeneity in IGB trials, regarding both methodological and clinical aspects. However, a co-adjuvant factor described by some authors in the loss and maintenance of weight has been the motivation and the encouragement to changing eating habits following a well-organized diet and a program of behavioural modification. The IGB alone and the technique of positioning appear to be safe. Despite the evidence for little additional benefit of the intragastric balloon in the loss of weight, its cost should be considered against a program of eating and behavioural modification."
"CD006245"
[ "16468111", "10856009", "2406126", "2044499" ]
[ "[Education of children with epilepsy and their parents by the modular education program epilepsy for families (FAMOSES)--results of an evaluation study].", "A randomized field trial of ACINDES: a child-centered training model for children with chronic illnesses (asthma and epilepsy).", "Randomized trial of a program to enhance the competencies of children with epilepsy.", "Impact of the Children's Epilepsy Program on parents." ]
[ "The aim of the study was to evaluate the efficacy of the modular educational program for children with epilepsy and their parents (FAMOSES). This program was developed by an interdisciplinary project group to improve knowledge, coping, treatment outcome, emotional and practical adaptation to the condition.\n A prospective, controlled, multi-center, pre-post study design was used to examine the efficacy of the program in the treatment group compared to the waiting group (control group). Questionnaires included epilepsy specific scales regarding knowledge, attitudes, restrictions in daily living, epilepsy related fears, coping with the chronic disease and generic instruments (quality of life, KINDL). 55 parents of the treatment group completed the questionnaires three months before the course and three months later; the corresponding waiting group included 48 parents. Respectively, 31 children, who participated in the program, completed the questionnaires immediately before the course and three months later; the corresponding waiting group included 19 children.\n Children, who attended the program, showed improvements in the domains perceived restrictions (significant, medium effect size), absence from school and seizure frequency. Not significantly greater compared to the control group were the improvements of knowledge, attitudes and fears regarding to the epilepsy. Parents of the treatment group showed significant enhancements in epilepsy specific knowledge (large effect size), attitudes toward the epilepsy, management of epileptic seizures and significant reductions of fears and restrictions of their child with epilepsy (small to medium effect sizes).", "A randomized field trial of a child-centered model of training for self-management of chronic illnesses was conducted of 355 Spanish-speaking school-aged children, between 6 and 15 years old, with moderate to severe asthma and epilepsy, in Buenos Aires, Argentina. The model, based on play techniques, consists of five weekly meetings of 8-10 families, with children's and parents' groups held simultaneously, coordinated by specially trained teachers and outside the hospital environment. Children are trained to assume a leading role in the management of their health; parents learn to be facilitators; and physicians provide guidance, acting as counselors. Group activities include games, drawings, stories, videos, and role-playing. Children and parents were interviewed at home before the program and 6 and 12 months after the program, and medical and school records were monitored for emergency and routine visits, hospitalizations, and school absenteeism. In asthma and epilepsy, children in the experiment showed significant improvements in knowledge, beliefs, attitudes, and behaviors compared to controls (probability of experimental gain over controls = .69 for epilepsy and .56 for asthma, with sigma2 = .007 and .016, respectively). Parent participants in the experiment had improved knowledge of asthma (39% before vs. 58% after) and epilepsy (22% before vs. 56% after), with a probability of gain = .62 (sigma2 = .0026) with respect to the control group. Similar positive outcomes were found in fears of child death (experimental 39% before vs. 4% after for asthma, 69% before vs. 30% after for epilepsy), as well as in disruption of family life and patient-physician relationship, while controls showed no change. Regarding clinical variables, for both asthma and epilepsy, children in the experimental group had significantly fewer crises than the controls after the groups (P = .036 and P = .026). Visits to physicians showed a significant decrease for those with asthma (P = .048), and emergency visits decreased for those with epilepsy (P = .046). An 18-item Children Health Locus of Control Scale (CHLCS) showed a significant increase in internality in experimental group children with asthma and epilepsy (P < .01), while controls did not change or performed worse 12 months after the program. School absenteeism was reduced significantly for those with asthma and epilepsy (for the group with asthma, fall/winter P = .006, and spring P = .029; for the group with epilepsy, P = .011).\n The program was successful in improving the health, activity, and quality of life of children with asthma and epilepsy. The data suggested that an autonomous (Piagetian) model of training is a key to this success, reinforcing children's autonomous decision making.", "A randomized, controlled trial was conducted in Santiago, Chile to test the impact of a child-centered, family-focused educational program for children aged 7-14 years with epilepsy and for their parents. The objectives of the program developed and pilot-tested in Los Angeles, California were to increase the children's knowledge, perceptions of competency, and skills related to dealing with seizures. Children in the experimental group (n = 123) and their parents separately attended four 1 1/2-h sessions and then met together at the end of each session to share learning experiences. Control children (n = 113) and their parents attended three 2-h sessions with a traditional lecture followed by question-and-answer format. All participants were pretested and then retested 5 months after completion of the educational intervention. Although there was some knowledge increase among children in the control group, the knowledge of children in the experimental group was significantly enhanced in a variety of areas related to management of their seizures and unnecessary restriction of their social and play activities. There was a significant increase in the self-perceptions of social competency of children in the experimental group. Children in the experimental group without serious behavioral problems also reported significantly better behavior after the intervention than did control children. There was no impact on children's disclosure of their diagnosis to friends and others.", "A randomized controlled trial was conducted in Santiago, Chile to test the efficacy of the Children's Epilepsy Program, a child-centered, family-focused intervention developed and pilot tested in Los Angeles, CA, U.S.A., using a counseling model for parents of children with seizure disorders to help them (a) deal with their anger, resentment, and grief related to the loss of a normal child; (b) increase their knowledge about caring for their child; (c) reduce anxieties related to having a child with a seizure disorder; and (d) improve their decision-making skills. All parents were pretested and then retested 5 months after the educational interventions. Parents in the experimental group (n = 185) and their children separately attended four 1 1/2-h sessions and then met together at the end of each session to share learning experiences. Comparison group parents (n = 180) and their children jointly attended three 2-h lecture sessions followed by question-and-answer periods. Although parents' overall knowledge of epilepsy was relatively high initially, it improved considerably in both comparison and experimental groups. With regard to anxiety, at the 5-month evaluation, experimental group parents and mothers in particular were more likely than control parents to state that they were less anxious (p less than 0.001), and their anxiety, as measured by the Taylor Manifest Anxiety scale, was significantly reduced (p less than 0.01)." ]
"While each of the programmes in this review showed some benefit to children with epilepsy their impacts were extremely variable. No programme showed benefits across the full range of outcomes. No study appears to have demonstrated any detrimental effects but the evidence in favour of any single programme is insufficient to make it possible to recommend one programme rather than another. More trials, carried out by independent research teams, are needed."
"CD008234"
[ "15072419", "18607963" ]
[ "Selective vestibular ablation by intratympanic gentamicin in patients with unilateral active Ménière's disease: a prospective, double-blind, placebo-controlled, randomized clinical trial.", "Intratympanic gentamicin therapy for control of vertigo in unilateral Menire's disease: a prospective, double-blind, randomized, placebo-controlled trial." ]
[ "To establish the efficacy of intratympanic gentamicin treatment in patients with unilateral Ménière's disease.\n This was a prospective, double-blind, randomized clinical trial of intratympanic gentamicin versus intratympanic buffer solution (placebo) in patients with established active Ménière's disease in the affected ear. Outcome measures included the number of vertiginous spells, degree of sensorineural hearing loss, labyrinthine function and labyrinthine asymmetry.\n Topical gentamicin provided a significant reduction in the number of vertiginous spells, although a \"placebo effect\" was also observed. Sensorineural hearing loss did not occur in the gentamicin group, although some deterioration occurred in the placebo group.\n Intratympanic gentamicin is a safe and efficient treatment for the vertiginous spells associated with Ménière's disease. When applied early in the course of the disease, it may prevent some of the sensorineural hearing deterioration associated with it.", "Intratympanic application of gentamicin is a relatively safe and efficient treatment for the reduction of complaints of vertigo attacks associated with Menière's disease. The treatment also reduces the severity of the perceived aural fullness.\n To investigate the effectiveness of intratympanic gentamicin treatment in patients with unilateral Menière's disease.\n In a prospective, double-blind, randomized, placebo-controlled clinical trial subjects scored vertigo complaints, aural fullness and tinnitus, before, during and up to 1 year after treatment. Hearing loss was monitored with pure tone audiometry.\n Gentamicin treatment resulted in a significant reduction of the score for vertigo complaints and the score for perceived aural fullness. A small increase in hearing loss (average 8 dB) was measured in the gentamicin group." ]
"Based on the results of the two included studies, intratympanic gentamicin seems to be an effective treatment for vertigo complaints in Ménière's disease, but carries a risk of hearing loss."
"CD008341"
[ "18383539", "19644849", "19560810", "19066176" ]
[ "Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study.", "Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis.", "Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial.", "Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study." ]
[ "To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX).\n Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo.\n The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P=0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P<0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group.\n Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX.", "To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA).\n MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1).\n An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P=0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P=0.049) and between group 3 (40.5%; P=0.038) but not group 4 (36.5%; P=0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively.\n Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.", "Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFalpha inhibitors.\n 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by interactive voice response system, stratified by study site and methotrexate use, to receive subcutaneous injections of placebo (n=155), 50 mg golimumab (n=153), or 100 mg golimumab (n=153) every 4 weeks between Feb 21, 2006, and Sept 26, 2007. Allocation was double-blind. Eligible patients had been treated with at least one dose of a TNFalpha inhibitor previously. Patients continued stable doses of methotrexate, sulfasalazine, hydroxychloroquine, oral corticosteroids, and non-steroidal anti-inflammatory drugs. The primary endpoint was achievement at week 14 of 20% or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis (ACR20). At week 16, patients who had less than 20% improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab, or from 50 mg to 100 mg golimumab. Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given. This study is registered with ClinicalTrials.gov, number NCT00299546.\n Patients had discontinued previous TNFalpha inhibitors because of lack of effectiveness (269 [58%] patients) or reasons unrelated to effectiveness (246 [53%] patients), such as intolerance and accessibility issues. Patients had active disease, which was indicated by a median of 14.0 (IQR 9.0-22.0) swollen and 26.0 (16.0-41.0) tender joints for the whole group. 28 (18%) patients on placebo, 54 (35%) patients on 50 mg golimumab (odds ratio 2.5 [95% CI 1.5-4.2], p=0.0006), and 58 (38%) patients on 100 mg golimumab (2.8 [1.6-4.7], p=0.0001) achieved ACR20 at week 14. Two patients were never treated, and 57 patients did not complete the study because of adverse events, unsatisfactory treatment effect, loss to follow-up, death, or other reasons. 155 patients on placebo, 153 on 50 mg golimumab, and 153 on 100 mg golimumab were assessed for drug efficacy. For weeks 1-16, serious adverse events were recorded in 11 (7%) patients on placebo, 8 (5%) on 50 mg golimumab, and 4 (3%) on 100 mg golimumab. For weeks 1-24, after some patients were given rescue therapy, serious adverse events were recorded in 15 (10%) patients on placebo, 14 (5%) on 50 mg golimumab, and 8 (4%) on 100 mg golimumab.\n Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNFalpha inhibitors.\n Centocor Research and Development and Schering-Plough Research Institute.", "The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.\n Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.\n The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.\n The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function." ]
"With an overall high grade of evidence, at the FDA-approved dose, golimumab is significantly more efficacious than placebo in treatment of patients with active RA , when used in combination with methotrexate. The short-term safety profile, based on short-term RCTs, is reasonable with no differences in total adverse events, serious infections, cancer, tuberculosis or deaths. Long-term surveillance studies are needed for safety assessment."
"CD003728"
[ "3679106" ]
[ "Group art therapy as an adjunct to treatment for chronic outpatients." ]
[ "Art therapy has lagged behind other therapeutic modalities in being subjected to rigorous evaluation of its effectiveness. This study examines psychosocial outcome for a group of chronic psychiatric outpatients. Half the patients were randomly assigned to a ten-week supportive art therapy group as an adjunct to treatment; the other patients served as a control group. Patients who remained in the art therapy group for the full ten weeks reported a significant improvement in their attitudes toward themselves as measured by the Progress Evaluation Scales, and their therapists rated them as significantly better able to get along with others. The authors believe the study demonstrates the potential of supportive art therapy to enhance functioning of chronic psychiatric patients in the short run. Empirical attention to long-term gains and to the efficacy of specific forms of art therapy is needed in the future." ]
"Randomised studies are possible in this field. Further evaluation of the use of art therapy for serious mental illnesses is needed as its benefits or harms remain unclear."
"CD003466"
[ "15772025", "6210163", "19106207", "7118759", "19635943", "19758364", "9474293", "15513722", "6181049" ]
[ "The effect of intervention on the free-play experience for mothers and their infants with developmental delay and cerebral palsy.", "Social interaction between parents and babies: validation of an intervention procedure.", "The effect of aided language stimulation on vocabulary acquisition in children with little or no functional speech.", "Programming \"loose training\" as a strategy to facilitate language generalization.", "Effects of it takes two to talk--the hanen program for parents of preschool children with cerebral palsy: findings from an exploratory study.", "Intensive speech and language therapy for older children with cerebral palsy: a systems approach.", "In-service training for schools on augmentative and alternative communication.", "Evaluating parent use of functional communication training to replace and enhance prelinguistic behaviours in six children with developmental and physical disabilities.", "Nonvocal language acquisition in adolescents with severe physical disabilities: Bliss symbol versus iconic stimulus formats." ]
[ "An intervention study designed to investigate the effects of one hour of maternal and infant behavior was conducted using experimental and control groups of mothers and their infants with cerebral palsy. Ten mother-infant pairs were in each group; infants ranged in age from 8-32 months. Infants of mothers in the control group received one hour of NDT-based occupational therapy. Two-factor repeated measures analysis of variance with repeated measures of the second factor indicated that the nonverbal instruction methods were significantly more successful in modifying maternal and infant behavior than were the verbal instruction methods. Implications of the results for intervention programs and future research were discussed.", "The purpose of this paper is to evaluate a set of intervention procedures developed as part of a parent-infant interaction model from a larger research study on social interaction between parents and their handicapped infants. Data is presented for three dyads, selected to illustrate the applicability of the procedures under a variety of different conditions including ages of the babies, target behaviours chosen and intervention situations. Results indicated that interactions could be altered through direct intervention with the mothers. The procedures used in the Social Interaction Assessment and Intervention model thus seem to be valid for bringing about change in interactions in dyads with a variety of interactive problems, in at least two different types of situations, and with babies differing widely in age and extent of delay.", "To describe the nature and frequency of the aided language stimulation program and determine the effects of a 3-week-long aided language stimulation program on the vocabulary acquisition skills of children with little or no functional speech (LNFS).\n Four children participated in this single-subject, multiple-probe study across activities. The aided language stimulation program comprised 3 activities: arts and crafts, food preparation, and story time activity. Each activity was repeated over the duration of 5 subsequent sessions. Eight target vocabulary items were taught within each activity. The acquisition of all 24 target items was probed throughout the duration of the 3-week intervention period.\n The frequency and nature of the aided language stimulation provided met the criterion of being used 70% of the time and providing aided language stimulation with an 80:20 ratio of statements to questions. The results indicated that all 4 participants acquired the target vocabulary items. There were, however, variations in the rate of acquisition.\n This study explores the impact of aided language stimulation on vocabulary acquisition in children. The most important clinical implication of this study is that a 3-week intervention program in aided language stimulation was sufficient to facilitate the comprehension of at least 24 vocabulary items in 4 children with LNFS.", "This study investigated the generalization of spontaneous complex language behavior across a nontraining setting and the durability of generalization as a result of programming and \"loose training\" strategy. A within-subject, across-behaviors multiple-baseline design was used to examine the performance of two moderately retarded students in the use of is/are across three syntactic structures (i.e., \"wh\" questions, \"yes/no\" reversal questions, and statements). The language training procedure used in this study represented a functional example of programming \"loose training.\" The procedure involved conducting concurrent language training within the context of an academic training task, and establishing a functional reduction in stimulus control by permitting the student to initiate a language response based on a wide array of naturally occurring stimulus events. Concurrent probes were conducted in the free play setting to assess the immediate generalization and the durability of the language behaviors. The results demonstrated that \"loose training\" was effective in establishing a specific set of language responses with the participants of this investigation. Further, both students demonstrated spontaneous use of the language behavior in the free play generalization setting and a trend was clearly evident for generalization to continue across time. Thus, the methods used appear to be successful for training the use of is/are in three syntactic structures.", "To investigate whether It Takes Two to Talk-The Hanen Program for Parents of Preschool Children With Cerebral Palsy is associated with change in interaction between children who have motor disorders and their parents.\n Eleven children aged 19-36 months who had nonprogressive motor disorders that affected their communication, and their mothers, were observed 4 months and 1 month before mothers attended It Takes Two to Talk training, and 1 month and 4 months after its completion.\n Interaction patterns were stable prior to training. After training, mothers initiated less and produced more responses and fewer requests. Children produced more initiations, as well as more requests and provisions of information, after training. Mothers' linguistic input did not change in amount or complexity. Changes were maintained 4 months later. Mothers' views of parenting did not change.\n It Takes Two to Talk may be associated with positive communication change for this group. Further investigation of its clinical effectiveness is warranted.", "To investigate whether speech therapy using a speech systems approach to controlling breath support, phonation, and speech rate can increase the speech intelligibility of children with dysarthria and cerebral palsy (CP).\n Sixteen children with dysarthria and CP participated in a modified time series design. Group characteristics were as follows: seven males, nine females; age range 12 to 18 years (mean 14y, SD 2); CP type: nine spastic, two dyskinetic, four mixed, one Worster-Drought; Gross Motor Function Classification System levels range I to V (median IV). Children received three 30- to 45-minute sessions of individual therapy per week for 6 weeks. Intelligibility in single words and connected speech was compared across four points: 1 week and 6 weeks before therapy, and 1 week and 6 weeks after its completion. Three familiar listeners and three unfamiliar listeners scored each recording. Mean percentage intelligibility was compared using general linear modelling techniques.\n After treatment, familiar listeners understood 14.7% more single words and 12.1% more words in connected speech. Unfamiliar listeners understood 15% more single words and 15.9% more words in connected speech after therapy.\n Therapy was associated with increases in speech intelligibility. Effects of the therapy should be investigated further, in an exploratory trial with younger children and in a randomized controlled trial.", "For children to progress in their use of augmentative communication systems, in-service training of staff in schools is required. This paper presents preliminary evaluation of a training package entitled 'My Turn to Speak'. Nineteen participants and 10 comparison staff were filmed before and after a five-session training workshop, interacting in the classroom in naturally occurring situations with a non-speaking physically disabled child. Significant improvements in the quality of adults' facilitation of the children's communication was discernible at follow-up, four months after completion of the training. However, teachers were found to alter their behaviour more quickly after training than non-teaching staff. The requirements for setting up successful multidisciplinary training are discussed.", "To evaluate parent use of functional communication training (FCT) to replace and enhance prelinguistic behaviours in six young children with developmental and physical disabilities.\n Initially, the communicative functions of the children's prelinguistic behaviours were assessed by parent interviews. Three communication functions were identified for each child and intervention goals to replace or enhance the child's existing prelinguistic behaviours were developed in consultation with parents. After a baseline phase, parents received training on implementation of FCT. Intervention was staggered across the three communicative functions in a multiple-probe design.\n Intervention was associated with increases in the replacement communication behaviour. Treatment gains were generally maintained at the monthly follow-ups.\n The results suggest that parents can use FCT to enhance communication skills in children with developmental and physical disabilities.", "This study compared training in two language systems for three severely handicapped, nonvocal adolescents: the Bliss symbol system and an iconic picture system. Following baseline, training and review trials were implemented using an alternating treatments design. Daily probes were conducted to assess maintenance, stimulus generalization, and response generalization, and data were collected on spontaneous usage of either language system throughout the school day. Results showed that students required approximately four times as many trials to acquire Bliss symbols as iconic pictures, and that students maintained a higher percentage of iconic pictures. Stimulus generalization occurred in both language systems, while the number of correct responses during responses generalization probes was much greater for the iconic system. Finally, students almost always showed more iconic responses than Bliss responses in daily spontaneous usage. These results suggest that an iconic system might be more readily spontaneous usage. These results suggest than an iconic system might be more readily acquired, maintained, and generalized to daily situations. Implications of these findings for the newly verbal person were discussed." ]
"Firm evidence of the positive effects of SLT for children with cerebral palsy has not been demonstrated by this review. However, positive trends in communication change were shown. No change in practice is recommended from this updated review. Further research is needed to describe this client group, and its possible clinical subgroups, and the methods of treatment currently used in SLT. Research is also needed to investigate the effectiveness of new and established interventions and their acceptability to families. Rigour in research practice needs to be extended to enable firm associations between therapy and the communication change to be made. There are now sufficient data to develop randomised controlled studies of dysarthria interventions and group parent training programmes. Such research is urgently needed to ensure clinically effective provision for this group of children, who are at severe risk of social and educational exclusion."
"CD002173"
[ "4398782", "1615179", "415495", "6810423", "4209680", "5004629", "3929698", "6230059", "4631823", "6791596", "806293", "413493", "3092689", "4101988", "10213547", "6775752", "5536092", "7979527", "5001717" ]
[ "Effect of cromolyn sodium on childhood asthma.", "Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up.", "The use of nebulised sodium cromoglycate in children.", "Nebulised sodium cromoglycate in the treatment of wheezy bronchitis in infants and young children.", "A \"double-blind\" trial of disodium cromoglycate in Thai asthmatic children.", "Treatment of children in an asthma centre with disodium cromoqlycate. Double-blind crossover trial.", "Nebulised sodium cromoglycate in recurrently wheezy preschool children.", "Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life.", "Effect of cromolyn sodium (disodium cromoglycate) on the peripheral eosinophilia of asthmatic children.", "Nebulised cromoglycate, theophylline, and placebo in preschool asthmatic children.", "Betamethasone 17 valerate aerosol and disodium chromoglycate in severe childhood asthma.", "Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial.", "Nebulised sodium cromoglycate in the treatment of wheezy bronchitis. A multicentre double-blind placebo controlled study.", "Disodium cromoglycate in pollen asthma.", "Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1-4-year-old children with moderate asthma.", "Controlled trial of cromoglycate and slow-release aminophylline in perennial childhood asthma.", "Disodium cromoglycate (intal) in the treatment of bronchial asthma in children.", "Efficacy of cromoglycate in persistently wheezing infants.", "Treatment of bronchial asthma with disodium cromoglycate (Intal) in children." ]
[ "nan", "Children born prematurely frequently have recurrent respiratory symptoms at follow-up and benefit from bronchodilator therapy. We have assessed if regular inhaled sodium cromoglycate would reduce this respiratory morbidity and need for bronchodilator therapy. Sixteen symptomatic children (median gestational age 29 weeks, post-natal age 15 months) were entered into a randomized double-blind, placebo-controlled trial. In two 3-week periods, the patients received either placebo or sodium cromoglycate (5 mg) as one puff q.d.s. from an inhaler via a coffee cup. Parents recorded their child's symptoms and need for bronchodilator therapy throughout and lung function was assessed by measurement of functional residual capacity (FRC) at the beginning and end of each 3-week period. The symptom score was reduced by 49% in the active compared to the placebo period (P less than 0.01) and bronchodilator was taken on a mean of 2.9 days per infant in the active period compared to 7.9 days in the placebo period (P less than 0.01). There was a significant improvement in FRC in ten of 16 patients over the active period but only in two infants over the placebo period (P less than 0.01). We conclude regular inhaled sodium cromoglycate is useful prophylaxis for symptomatic pre-term children.", "nan", "44 children under 2 years of age suffering from recurrent or persistent wheezy bronchitis, completed a double-blind crossover trial comparing nebulised sodium cromoglycate and matching placebo. Analysis showed that treatment response was age-related. Sodium cromoglycate proved significantly superior to placebo in reducing night cough, sleep disturbance, wheeze and activity limitation in the 24 patients aged 12 months and above (mean 17.3) on entry to the study. Whereas no significant differences were observed in the 20 children below 12 months of age (mean 8.3). These findings were confirmed by weekly clinical assessment. Both age groups spent fewer days in hospital during the active treatment period. Final subjective assessments showed that the older age group, parents favoured cromoglycate treatment, whereas in the younger age group, parents favoured placebo, although neither reached statistical significance. Both age groups showed marked placebo response to nebulised water.", "nan", "nan", "A double blind crossover study of nebulised sodium cromoglycate in 27 asthmatic preschool children was carried out over a one year period. All subjects had sufficiently severe asthma to have had at least one admission to hospital. The active treatment was sodium cromoglycate 20 mg (in 2 ml) administered by a nebuliser four times daily. Assessment was made by a diary card and clinical examination. Results were analysed in 24 subjects who completed the study. Statistical analysis allowed for order of treatment and seasonal effects. Significant results in favour of treatment with sodium cromoglycate were obtained for night cough, day activity, percentage of symptom free days, and overall severity of asthma. During active treatment there was no reduction in the rate of admissions to hospital or intravenous drugs used. The wheeze score during the week after an upper respiratory tract infection was not reduced during treatment with sodium cromoglycate. Nebulised sodium cromoglycate is a tedious prophylactic treatment for the young asthmatic child but is useful when other treatments have failed.", "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.", "nan", "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.", "Eleven children with severe perennial asthma and a poor clinical response to disodium cromoglycate were studied in a 4-month, double blind trial involving 1 month's treatment with placebo, disodium cromoglycate, betamethasone 17 valerate, and both drugs combined according to a predetermined random design. Each drug apparently reduced symptoms and improved daily peak flow and fortnightly spirometric measurements compared with placebo, but the improvement after betamethasone 17 valerate was greater in part because of the way this group of patients was selected. There did not appear to be any additional benefit when both drugs were used together. Betamethasone 17 valerate was not compared with beclomethasone diproprionate aerosol and there is no reason to believe it may be superior. Corticosteroid aerosols have potential hazards which may prove to equal those of long-term systemic steroids, but they offer the prospect of satisfactory control of symptoms without the risk of growth suppression in children with severe asthma. Disodium cromoglycate remains the drug of choice in severe childhood asthma and the use of corticosteroid aerosols should be confined to those children who fail to respond satisfactorily to disodium cromoglycate.", "Seventeen asthmatic children under 5 years of age took part in a double-blind controlled trial of nebulized sodium cromoglycate solution. Daily symptom scores kept by the parents showed improvement in 11 children during active treatment, and a significant improvement in scores for cough by day and night was obtained for the group as a whole.", "The efficacy of nebulised sodium cromoglycate (SCG) used as a prophylactic treatment of wheezy bronchitis in children aged 1 to 4 years was evaluated in a multicentre double-blind placebo controlled, group comparative study. Fifty-four patients completed the 10-week trial (29 treated with SCG and 25 treated with placebo), preceded by 4-8 weeks baseline. Nebulised SCG did not prove significantly superior to placebo in reducing day wheezing, day coughing, or sleep disturbance due to wheezing or coughing at night. Neither was there significant difference in the use of supportive medicine (beta 2-agonist and theophylline) between the groups. Extra doctor visits, hospital admissions, and parental preference did not show significant difference either.", "nan", "Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children. The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children. We studied the feasibility and effects of this therapy compared with placebo in children aged 1-4 years.\n 218 children aged 1-4 years with moderate asthma were recruited through 151 general practitioners between March, 1995, and March, 1996. They were randomly assigned sodium cromoglycate (10 mg three times daily) or placebo, given by inhaler with spacer device and face-mask for 5 months. Rescue medication (ipratropium plus fenoterol aerosol) was available during the baseline period of 1 month and the intervention period. Parents completed a daily symptom-score list. The primary outcome measure was the proportion of symptom-free days in months 2 to 5. Analysis was by both intention to treat and on treatment.\n 167 (77%) children completed the trial. 131 (78%) of these children used at least 80% of the recommended dose. Of the 51 children who stopped prematurely, 23 had difficulties with inhaled treatment. The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period (95% CI for mean difference 5.1 to 17.5 cromoglycate, 11.9 to 23.3 placebo). However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days (mean 65.7 [SD 25.3] vs 64.3 [24.5]%; 95% CI for difference -8.46 to 5.70) or in any other outcome measure.\n Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years. However, long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group.", "nan", "nan", "A prospective study was undertaken to evaluate the efficacy of (sodium) cromoglycate in the treatment of persistent wheezing in 31 children between 4 and 12 months of age. The subjects were randomised to receive either 40 mg of cromoglycate (n = 16) or physiological saline as placebo (n = 15) three times a day by wet nebulisation in a double blind fashion for a period of six weeks. The patients were evaluated with daily symptom scores and respiratory function testing measuring maximal expiratory flow at functional residual capacity (VmaxFRC) before initiating treatment and upon completion. At baseline, mean (SD) symptom scores between the two groups were comparable (cromoglycate 99.5 (29.8), placebo 104.5 (29.7)) as were VmaxFRC expressed as per cent of predicted normals (cromoglycate 48 (28), placebo 46 (20)). Upon completion of the treatment protocol, no significant difference could be found between the two groups for either symptom score (cromoglycate 67.6 (40.2), placebo 58.6 (41.4)), or VmaxFRC (cromoglycate 52 (24), placebo 60 (32)). It is concluded, therefore, that 40 mg of cromoglycate three times a day administered via facemask and wet nebulisation was no more effective than placebo in the treatment of our sample of persistently wheezing infants under 1 year of age.", "nan" ]
"There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma."
"CD002886"
[ "2882288", "2267922", "10503682", "8135557", "3302924", "7359263" ]
[ "Effect of a single oral dose of prednisolone in acute childhood asthma.", "Placebo controlled trial of systemic corticosteroids in acute childhood asthma.", "Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma.", "Prednisolone and salbutamol in the hospital treatment of acute asthma.", "Intravenous methylprednisolone efficacy in status asthmaticus of childhood.", "Corticosteroids in status asthmaticus." ]
[ "140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care.", "In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.", "The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.", "The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.", "Forty-nine nonsteroid-dependent children hospitalized with status asthmaticus were randomized to receive IV placebo or methylprednisolone treatment (1 mg/kg every six hours). All patients received nebulized isoetharine inhalations and continuous IV aminophylline infusion. Twenty-four hours after admission, the methylprednisolone-treated patients demonstrated a greater rate of improvement in their clinical scoring index than did placebo-treated children. However, the duration of hospital stay was not significantly shortened. Twenty-eight of the patients performed serial bedside spirometry at 0, 12, 24, and 36 hours after admission. The methyl-prednisolone-treated patients experienced a more rapid recovery from peripheral airway obstruction as measured by forced expiratory flow rate during 25% to 75% of forced vital capacity (FEF25-75). The magnitude and rate of improvement in FEF25-75 was significantly greater at 36 hours (P less than .05) and independent of changes in peak expiratory flow rate, forced vital capacity, or forced expiratory volume in the first second of forced vital capacity. Placebo-treated patients had a higher incidence of asthma relapse within 4 weeks of discharge (eight v two relapses, P less than .05). Findings of this study indicate that IV corticosteroid therapy is beneficial in treating pediatric status asthmaticus.", "Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents." ]
"Systemic corticosteroids produce some improvements for children admitted to hospital with acute asthma. The benefits may include earlier discharge and fewer relapses. Inhaled or nebulised corticosteroids cannot be recommended as equivalent to systemic steroids at this time. Further studies examining differing doses and routes of administration for corticosteroids will clarify the optimal therapy."
"CD006769"
[ "11078836" ]
[ "Amniotic membrane transplantation for repair of leaking glaucoma filtering blebs." ]
[ "To compare the safety and efficacy of human preserved amniotic membrane transplant with conjunctival advancement for repair of late-onset glaucoma filtering bleb leaks.\n A prospective, randomized clinical trial compared amniotic membrane transplant with conjunctival advancement in patients with leaking glaucoma filtering blebs. Intraocular pressure, number of glaucoma medications, and reoperation for glaucoma or persistent or recurrent bleb-leak were compared in the two groups. Patients were followed for a minimum of 1 year.\n Mean intraocular pressure was the same at 6 (amniotic membrane transplant, 15.4 +/- 4.4, conjunctival advancement 14.1 +/- 6.4, P = 0.6), 12 (amniotic membrane transplant, 15.0 +/- 6.3, conjunctival advancement, 13.2 +/- 6.6, P = 0.5), and 24 (amniotic membrane transplant, 17.2 +/- 7.1, conjunctival advancement, 15.0 +/- 6.3, P = 0.6) months. The mean number of glaucoma medications in use was the same in the two groups at all time intervals. After an average follow-up of 19 months, there were seven failures in the amniotic membrane transplant group (two with persistent leaks that were unresponsive to further suturing, two with late-onset leaks, and three who required repeat glaucoma surgery) and none in the conjunctival advancement group. The cumulative survival rate for amniotic membrane transplant was 81% at 6 months, 74% at 1 year, and 46% at 2 years. The cumulative survival rate was 100% for conjunctival advancement throughout follow-up.\n Amniotic membrane transplantation does not offer an effective alternative to conjunctival advancement for repair of leaking glaucoma filtering blebs." ]
"Although a variety of treatments have been proposed for bleb leaks, there is no evidence of their comparative effectiveness. The evidence in this review was provided by a single trial that compared two surgical procedures (conjunctival advancement and amniotic membrane transplant). The trial did show a superiority of conjunctival advancement, which was regarded as standard treatment, to amniotic membrane transplantation. There is a need for more randomised trials to validate the findings of this single trial and provide more information on the different types of interventions, especially non-surgical treatments compared to surgical procedures. We recommend that any intervention should be compared to a standard procedure, which is to date conjunctival advancement."
"CD005573"
[ "10466665", "15507864", "15647189", "15569116" ]
[ "Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial.", "Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis.", "Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial.", "Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis." ]
[ "Ulcerative colitis has been suggested to be caused by infection and there is circumstantial evidence linking Escherichia coli with the condition. Our aim was to find out whether the administration of a non-pathogenic strain of E. coli (Nissle 1917) was as effective as mesalazine in preventing relapse of ulcerative colitis. We also examined whether the addition of E. coli to standard medical therapy increased the chance of remission of active ulcerative colitis.\n This was a single-centre, randomised, double-dummy study in which 120 patients with active ulcerative colitis were invited to take part. 116 patients accepted; 59 were randomised to mesalazine and 57 to E. coli. All patients also received standard medical therapy together with a 1-week course of oral gentamicin. After remission, patients were maintained on either mesalazine or E. coli and followed up for a maximum of 12 months. A two-stage, conditional, intention-to-treat analysis was done.\n 44 (75%) patients in the mesalazine group attained remission compared with 39 (68%) in the E. coli group. Mean time to remission was 44 days (median 42) in the mesalazine group and 42 days (median 37) for those treated with E. coli. In the mesalazine group, 32 (73%) patients relapsed compared with 26 (67%) in the E. coli group. Mean duration of remission was 206 days in the mesalazine group (median 175) and 221 days (median 185) in the E. coli group.\n Our results suggest that treatment with a non-pathogenic E. coli has an equivalent effect to mesalazine in maintaining remission of ulcerative colitis. The beneficial effect of live E. coli may provide clues to the cause of ulcerative colitis.", "Balsalazide is well tolerated and effective in treating acute ulcerative colitis. VSL#3 is a probiotic cocktail proven to be effective in preventing flare-ups of chronic pouchitis. We compared the efficacy and safety of low-dose balsalazide (2.25 g/day) plus 3 g/day VLS#3 (group A) with medium-dose balsalazide alone (group B) and with mesalazine (group C) in the treatment of mild-to-moderate active ulcerative colitis.\n Ninety patients (30 per group) were randomly enrolled, with a treatment duration of 8 weeks. Efficacy was assessed by symptoms assessment, endoscopic appearance, and histological evaluation.\n Balsalazide/VSL#3 was significantly superior to balsalazide alone and to mesalazine in obtaining remission: 24 patients of group A were in remission [per-protocol: 85.71% (C.I.95%: 62-96), on intention-to-treat: 80% (C.I.95%: 59-91)], while 21 group B [per-protocol: 80.77% (C.I. 95%: 51-82), on intention-to-treat: 77% (C.I.95%: 43-81)] and 16 group C patients [per-protocol: 72.73% (C.I. 95%: 30-75), on intention-to-treat: 53.33% (C.I.95%: 42-62)] were in remission (p<0.02). Balsalazide with or without VSL#3 was better tolerated than mesalazine: two group C patients were withdrawn from the study because of severe side-effects; 1 group A (3.33%), 3 group B (10%) and 4 group C (13.33%) patients experienced slight side-effects. The balsalazide/VSL#3 combination was faster in obtaining remission than balsalazide alone or mesalazine (4, 7.5, and 13 days in groups A, B and C, respectively) and also better in improving all parameters evaluated.\n Balsalazide/VSL#3 may be a very good choice in the treatment of active mild-to-moderate active ulcerative colitis instead of balsalazide alone or mesalazine.", "Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state.\n A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured.\n Sigmoidoscopy scores (scale 0-6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p=0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p=0.016, 0.038, and 0.008, respectively). Tumour necrosis factor alpha and interleukin 1alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p=0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue.\n Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.", "Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.\n To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis.\n Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment.\n Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group.\n Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results." ]
"Conventional therapy combined with a probiotic does not improve overall remission rates in patients with mild to moderate ulcerative colitis. However, there is limited evidence that probiotics added to standard therapy may provide modest benefits in terms of reduction of disease activity in patients with mild to moderately severe ulcerative colitis. Whether probiotics are as effective in patients with severe and more extensive disease and whether they can be used as an alternative to existing therapies is unknown. Further well designed, larger randomised controlled trials are needed to determine whether probiotics can be used as an alternative to current treatment modalities."
"CD005976"
[ "12243918", "15070633" ]
[ "Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial.", "Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial." ]
[ "For most infections, especially acute respiratory infections (ARIs), the recommended duration of therapy is not based on strong scientific or clinical criteria. Shorter courses of antibiotics for non-severe pneumonia would result in lower costs, enhance patient compliance, and might help to contain antimicrobial resistance. We aimed to compare the clinical efficacy of 3-day and 5-day courses of amoxicillin in children with non-severe pneumonia.\n We recruited 2000 children, aged 2-59 months, with non-severe pneumonia (WHO criteria) diagnosed in the outpatient departments of seven hospitals. Patients were randomly assigned to 3 days or 5 days of treatment with oral amoxicillin. The primary outcome was treatment failure. Analyses were by intention to treat.\n We allocated 1000 children to 3 days of treatment and 1000 to 5 days. Treatment failed in 209 (21%) patients in the 3-day group, and in 202 (20%) in the 5-day group (difference 0.7%; 95% CI -1.8 to 3.2). In 12 (1%) children in the 3-day group and in 13 (1%) in the 5-day group the disease relapsed (difference 0.1%; -0.6 to 0.8). Treatment was more likely to fail in children who did not adhere to treatment (p<0.0001), in those younger than 12 months (p<0.0001), in those whose illness lasted for 3 days or longer (p=0.004), in those whose respiratory rate was more than 10 breaths/min above the age-specific cut-off (p=0.004), and in those with vomiting (p=0.009). Non-adherence was also associated with failure of treatment in the 5-day group (p<0.0001).\n Treatment with oral amoxicillin for 3-days was equally as effective as treatment for 5 days in children with non-severe pneumonia. The most important risk factor for treatment failure was non-compliance, which was also associated with longer duration of therapy.", "To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children.\n Randomised, double blind, placebo controlled multicentre trial.\n Outpatient departments of seven referral hospitals in India.\n 2188 children aged 2-59 months, 1095 given three days of treatment and 1093 given five days.\n Oral amoxicillin 31-54 mg/kg/day in three divided doses.\n Treatment failure: defined as development of chest indrawing, convulsions, drowsiness, or inability to drink at any time; respiratory rate above age specific cut points on day 3 or later; or oxygen saturation by pulse oximetry < 90% on day 3.\n The clinical cure rates with three days and five days of treatment were 89.5% and 89.9%, respectively (absolute difference 0.4 (95% confidence interval--2.1 to 3.0)). Adherence to treatment regimen was 94% and 85% for three day and five day treatments, respectively. Loss to follow up was 5.4% by day 5. There were no deaths, 41 hospitalisations, and 36 minor adverse reactions. There were 225 (10.3%) clinical failures and 106 (5.3%) relapses, and rates were similar in both treatments. At enrollment, 513 (23.4%) children tested positive for respiratory syncytial virus, and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 (40.4%) and 496 (22.8%) children, respectively. Clinical failure was associated with isolation of respiratory syncytial virus (adjusted odds ratio 1.95 (95% confidence interval 1.0 to 3.8)), excess respiratory rate of > 10 breaths/minute (2.89 (1.83 to 4.55)), and non-adherence with treatment at day 5 (11.57 (7.4 to 18.0)).\n Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia." ]
"The evidence of this review suggests that a short course (three days) of antibiotic therapy is as effective as a longer treatment (five days) for non-severe CAP in children under five years of age. However, there is a need for more well-designed RCTs to support our review findings."
"CD001289"
[ "8756815", "9596315", "1745841" ]
[ "Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.", "Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group.", "Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo." ]
[ "We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.", "To study the safety and efficacy of aerosolized recombinant human DNase I in the treatment of idiopathic bronchiectasis.\n Double-blind, randomized, placebo-controlled, multicenter study.\n Three hundred forty-nine adult outpatients in stable condition with idiopathic bronchiectasis from 23 centers in North America, Great Britain, and Ireland.\n Study patients received aerosolized rhDNase or placebo twice daily for 24 weeks. Primary end points were incidence of pulmonary exacerbations and mean percent change in FEV1 from baseline over the treatment period.\n Pulmonary exacerbations were more frequent and FEV1 decline was greater in patients who received rhDNase compared with placebo during this 24-week trial.\n rhDNase was ineffective and potentially harmful in this group of adult outpatients in stable condition with idiopathic bronchiectasis. This contrasts with previously published results that demonstrated efficacy of rhDNase in patients with cystic fibrosis bronchiectasis.", "The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious." ]
"There is not enough evidence to evaluate the routine use of mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance."
"CD006189"
[ "15727375", "3730737", "13160496", "7236953", "15479896" ]
[ "Frozen shoulder syndrome: comparison of oral route corticosteroid and intra-articular corticosteroid injection.", "A controlled study of oral prednisolone in frozen shoulder.", "Oral cortisone therapy in periarthritis of the shoulder; a controlled trial.", "The upper limb: the frozen shoulder.", "Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double blind, placebo controlled trial." ]
[ "Twenty-six patients with frozen shoulder syndrome (Stage 2 and 3) were included in this study conducted at Dr. Kariadi General Hospital, Semarang, Indonesia and randomly allocated into 2 groups: 40 mg triamcinolone intra-articular injection and triamcinolone oral tablets. The result showed that triamcinolone intra-articular injection group \"cured\" rate was 5.8 times higher at week one compared to the triamcinolone tablet group. Sixty-two percent of the cases with triamcinolone intra-articular injection achieved their \"cured\" condition after one week of therapy, compared with only 14% of the triamcinolone tablets group. We conclude that, intra-articular corticosteroid injection provide faster improvement compared to oral route.", "Forty patients with frozen shoulder were randomly allocated to a treated group who received oral prednisolone or a nontreatment group who received no specific therapy. All the patients were encouraged to perform home pendular exercise. The improvement in pain at night showed a significantly different pattern in the two groups (p less than 0.05), with the treated group improving more rapidly. Pain on movement and at rest and the recovery in the range of movement was not significantly different in the two groups. There was no difference between the patient groups at the end of the study (8 months follow-up) and patients still had a marked restriction in range (p less than 0.0001) when compared to normal controls of similar age and sex.", "nan", "nan", "To determine whether a short course of prednisolone is superior to placebo for improving pain, function, and range of motion in adhesive capsulitis.\n Double blind, randomised, placebo controlled trial.\n Community based rheumatology practice in Australia.\n 50 participants (24 active, 26 placebo); 46 completed the 12 week protocol. Entry criteria were age > or =18 years, pain and stiffness in predominantly one shoulder for > or =3 weeks, and restriction of passive motion by >30 degrees in two or more planes.Interventions: 30 mg oral prednisolone/day for three weeks or placebo.\n Overall, night, and activity related pain, SPADI, Croft shoulder disability questionnaire, DASH, HAQ, SF-36, participant rated improvement, and range of active motion measured at baseline and at 3, 6, and 12 weeks.\n At 3 weeks, there was greater improvement in overall pain in the prednisolone group than in the placebo group (mean (SD) change from baseline, 4.1 (2.3) v 1.4 (2.3); adjusted difference in mean change between the two groups, 2.4 (95% CI, 1.1 to 3.8)). There was also greater improvement in disability, range of active motion, and participant rated improvement (marked or moderate overall improvement in 22/23 v 11/23; RR = 2 (1.3 to 3.1), p = 0.001). At 6 weeks the analysis favoured the prednisolone group for most outcomes but none of the differences was significant. At 12 weeks, the analysis tended to favour the placebo group.\n A three week course of 30 mg prednisolone daily is of significant short term benefit in adhesive capsulitis but benefits are not maintained beyond six weeks." ]
"Available data from two placebo-controlled trials and one no-treatment controlled trial provides "Silver" level evidence (www.cochranemsk.org) that oral steroids provides significant short-term benefits in pain, range of movement of the shoulder and function in adhesive capsulitis but the effect may not be maintained beyond six weeks."
"CD009043"
[ "19797985", "19948625" ]
[ "A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.", "Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder." ]
[ "To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.\n Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed.\n At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p < .05). All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8. Discontinuation rates due to adverse events were as follows: placebo 7.7%, aripiprazole 5 mg/day 9.4%, 10 mg/day 13.6%, and 15 mg/day 7.4%. The most common adverse event leading to discontinuation was sedation. There were two serious adverse events: presyncope (5 mg/day) and aggression (10 mg/day). At week 8, mean weight change (last observation carried forward) was as follows: placebo +0.3 kg, aripiprazole 5 mg/day +1.3 kg, 10 mg/day +1.3 kg, and 15 mg/day +1.5 kg; all p < .05 versus placebo.\n Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder.", "The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these.\n This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6-17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression-Improvement score (CGI-I). Safety and tolerability were also assessed.\n Ninety-eight patients were randomly assigned to receive placebo (n = 51) or aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8.\n Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated." ]
"Evidence from two randomized controlled trials suggests that aripiprazole can be effective in treating some behavioral aspects of ASD in children. After treatment with aripiprazole, children showed less irritability, hyperactivity, and stereotypies (repetitive, purposeless actions). Notable side effects must be considered, however, such as weight gain, sedation, drooling, and tremor. Longer studies of aripiprazole in individuals with ASD would be useful to gain information on long-term safety and efficacy."
"CD003582"
[ "10629368" ]
[ "Clinical trial of induction of labor versus expectant management in twin pregnancy." ]
[ "The appropriate date of delivery in twin pregnancies is supposed to be earlier than that in singleton pregnancy. The aim of this study was to compare two strategies for managing twin pregnancies (i.e., immediate induction and expectant management).\n Seventeen patients underwent immediately induced labor by administration of oral prostaglandin E(2) at 37 weeks, while 19 patients underwent expectant management.\n The average gestational age at delivery in the induction group was 37.5 +/- 0.4 weeks, significantly earlier than that in the expectant management group (39.0 +/- 1.1 weeks). However, there were no significant differences in the average birth weight between the two groups (2, 700 +/- 330 g in the induction group vs. 2,672 +/- 392 g in the expectant management group). The cesarean delivery rate in the induction group was 18%, not significantly different from that in the expectant management group (32%). The most common indication for cesarean section in the expectant management group was maternal infection, while there was no maternal infection in the induction group (p = 0.08).\n It may be acceptable do intervene in twin pregnancies earlier than in singleton pregnancies during term.\n Copyright 2000 S. Karger AG, Basel" ]
"The small trial identified was underpowered to detect the outcome measures of interest. Consequently, there are insufficient data available to support a practice of elective delivery from 37 weeks' gestation for women with an otherwise uncomplicated twin pregnancy at term."
"CD004765"
[ "2460414" ]
[ "Dye laser photocoagulation of macular subretinal neovascularization in pathological myopia. A randomized study of three different wavelengths." ]
[ "The authors present a randomized study of 27 eyes affected by pathological myopia with macular subretinal neovascularization which were treated with a tunable dye laser. The effectiveness of three different wavelengths (577, 590 and 620 nm) in the direct treatment of subretinal neovascularizations was evaluated in 3 groups of 9 patients each. Statistical analysis of both visual and anatomical results did not show significant differences among the three wavelengths used." ]
"Despite its use over several years the effectiveness of laser photocoagulation for myopic CNV has not been established. Although there was a suggestion of short-term effectiveness in one small study on non-subfoveal CNV the results were potentially biased. Observational studies suggest that the enlargement of the atrophic laser scar after laser treatment of non-subfoveal CNV could be a potentially vision-threatening long-term complication, even in eyes free of CNV recurrence."
"CD003685"
[ "10566565", "11087881" ]
[ "The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis. Phase II Rofecoxib Rheumatoid Arthritis Study Group.", "Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group." ]
[ "Nonsteroidal anti-inflammatory drugs. (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response (P = 0.025 and 0.001 vs. placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index (P<0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy (P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA.", "Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis.\n We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers).\n Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups.\n In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor." ]
"In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear. Rofecoxib was voluntarily withdrawn from global markets in October 2004. It cannot therefore be prescribed and therefore there are no implications for practice concerning its use. None the less when considering which NSAID to use, it must be borne in mind that the toxicity of NSAIDs is variable amongst patients and drugs and it tends to be dose related and associated with variation in the mode of action, absorption, distribution and metabolism.There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing. It is likely that this issue will not be resolved until research has enabled a fuller understanding of the complex mechanism by which the Cox system operates."
"CD003438"
[ "3769894", "18074710", "18853562", "5262986", "5810168", "15530927", "8799442", "16435703" ]
[ "Can the conspicuity of objects be predicted from laboratory experiments?", "Effects of age and illumination on night driving: a road test.", "Highlighting human form and motion information enhances the conspicuity of pedestrians at night.", "Actual pedestrian visibility and the pedestrian's estimate of his own visibility.", "Safety clothing for human traffic obstacles.", "High visibility safety apparel and nighttime conspicuity of pedestrians in work zones.", "Effects of retroreflector positioning on nighttime recognition of pedestrians.", "Limitations in drivers' ability to recognize pedestrians at night." ]
[ "nan", "This study investigated the effects of drivers' age and low light on speed, lane keeping, and visual recognition of typical roadway stimuli.\n Poor visibility, which is exacerbated by age-related changes in vision, is a leading contributor to fatal nighttime crashes. There is little evidence, however, concerning the extent to which drivers recognize and compensate for their visual limitations at night.\n Young, middle-aged, and elder participants drove on a closed road course in day and night conditions at a \"comfortable\" speed without speedometer information. During night tests, headlight intensity was varied over a range of 1.5 log units using neutral density filters.\n Average speed and recognition of road signs decreased significantly as functions of increased age and reduced illumination. Recognition of pedestrians at night was significantly enhanced by retroreflective markings of limb joints as compared with markings of the torso, and this benefit was greater for middle-aged and elder drivers. Lane keeping showed nonlinear effects of lighting, which interacted with task conditions and drivers' lateral bias, indicating that older drivers drove more cautiously in low light.\n Consistent with the hypothesis that drivers misjudge their visual abilities at night, participants of all age groups failed to compensate fully for diminished visual recognition abilities in low light, although older drivers behaved more cautiously than the younger groups.\n These findings highlight the importance of educating all road users about the limitations of night vision and provide new evidence that retroreflective markings of the limbs can be of great benefit to pedestrians' safety at night.", "Exploring how biological motion can make pedestrians more conspicuous to drivers at night, one-hundred-and-twenty participants were driven along an open-road route at night and pressed a button whenever they recognized that a pedestrian was present. A test pedestrian wearing black clothing alone or with 302 cm2 of retroreflective markings in one of four configurations either stood still or walked in place on an unilluminated sidewalk. Participants' response distances were maximal for the full biological-motion configuration and remained surprisingly long when convenient subsets of reflective markers were positioned on the pedestrian's ankles and wrists. When the pedestrian wore a reflective vest, the responses were no better than when he wore no reflective markings. The biological-motion advantage actually results from interacting form-perception and motion-perception mechanisms. These results confirm that basic perceptual phenomena-observers' sensitivity to human form and motion can be harnessed to reduce an important problem of traffic safety.", "nan", "nan", "Every year numerous occupational fatalities result from pedestrians being struck by motor vehicles intruding into work zones.\n Attributes of retroreflective personal safety garments on pedestrian conspicuity at night were assessed in a field study. Using instrumented vehicles on a closed track, participants drove through simulated work zones attempting to detect pedestrians located in the work zones.\n Configuration of the retroreflective trim, trim color, placement in the work zone, and driver age significantly affected pedestrian conspicuity. Intensity and the amount of retroreflective trim did not.\n Personal safety garments incorporating retroreflective trim significantly improve pedestrian conspicuity in work zones.\n The results emphasize the importance of retroreflective trim on personal safety garments, particularly if the trim is located on garment sleeves.\n We examine the design attributes that contribute to making a personal safety garment conspicuous. The results have implications regarding preferred garment designs, industry standards, and service life of personal safety garments.", "This field study investigated potential effects of retroreflector positioning on recognition of nighttime pedestrians. The subject's task was to press a response button whenever he/she recognized a pedestrian on or alongside the road, while in a car with low-beam lamps on that was driven at a constant speed on a dark road. The results showed that each retroreflector configuration yielded significantly longer recognition distances than the no-retroreflector configuration. More importantly, the retroreflective markings attached to the limbs led to significantly longer (about 60-80%) recognition distances than when the retroreflective markings were attached to the torso. Furthermore, a pedestrian was more recognizable while crossing the road than while approaching the subject vehicle, except for configurations involving no retroreflective markings.", "This study quantified drivers' ability to recognize pedestrians at night. Ten young and 10 older participants drove around a closed road circuit and responded when they first recognized a pedestrian. Four pedestrian clothing and two beam conditions were tested. Results demonstrate that driver age, clothing configuration, headlamp beam, and glare all significantly affect performance. Drivers recognized only 5% of pedestrians in the most challenging condition (low beams, black clothing, glare), whereas drivers recognized 100% of the pedestrians who wore retroreflective clothing configured to depict biological motion (no glare). In the absence of glare, mean recognition distances varied from 0.0 m (older drivers, low beam, black clothing) to 220 m (722 feet; younger drivers, high beam, retroreflective biomotion). These data provide new motivation to minimize interactions between vehicular and pedestrian traffic at night and suggest garment designs to maximize pedestrian conspicuity when these interactions are unavoidable." ]
"Visibility aids have the potential to increase visibility and enable drivers to detect pedestrians and cyclists earlier. Biomotion markings, which highlight the movement and form of the pedestrian, showed evidence of improving pedestrians' conspicuity at night. Public acceptability of various effective strategies which improve visibility would merit further development. However, the effect of visibility aids on pedestrian and cyclist safety remains unknown. A cluster randomised controlled trial involving large communities may provide an answer to this question. It would, however, be a challenging trial to conduct. Studies that collect data of road traffic injuries relating to the use of visibility aids also warrant consideration."
"CD007825"
[ "22054336", "21487425", "18519821", "11994884", "17116916", "16918861", "16267182", "18606949", "15823886", "21680632", "16253541" ]
[ "Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial.", "Effectiveness of a multi-disciplinary family-based programme for treating childhood obesity (the Family Project).", "Prevention of negative symptom psychopathologies in first-episode schizophrenia: two-year effects of reducing the duration of untreated psychosis.", "Care management, dementia care and specialist mental health services: an evaluation.", "The effect of a disease management intervention on quality and outcomes of dementia care: a randomized, controlled trial.", "Using school staff to establish a preventive network of care to improve elementary school students' control of asthma.", "A whole system study of intermediate care services for older people.", "Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial.", "Interdisciplinary collaboration between primary care, social insurance and social services in the rehabilitation of people with musculoskeletal disorder: effects on self-rated health and physical performance.", "Effectiveness of anonymised information sharing and use in health service, police, and local government partnership for preventing violence related injury: experimental study and time series analysis.", "Impact evaluation of a Dutch community intervention to improve health-related behaviour in deprived neighbourhoods." ]
[ "Few robust studies have tested whether enhancing housing also improves health.\n To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.\n Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.\n A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.\n The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.\n This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.", "To determine if a multi-component family focused education package is more effective than a waiting list control group in treating overweight and obese children.\n A 2-year randomised controlled trial; 65 overweight and obese children aged 6-14 years were allocated to active intervention in either the first or second year, with body composition monitoring alone in the control period. Anthropometric measurements were undertaken at six monthly intervals and a 7-day food and activity diary were issued.\n Over the 2 years of the study body mass index (BMI) SDS (z score) fell significantly in the intervention/control (I/C) group, but not in the control/intervention (C/I) group. The difference between groups was 0.3, which was borderline significant (95% confidence interval (95% CI) -0.62 to 0.02, P=0.06) before adjusting for potential confounding factors. Thirty-three percent of the I/C group and 12% of the C/I group achieved the target reduction of 0.5 BMI SDS. The I/C group had a significantly greater reduction in the percentage with a BMI above the 99.6th centile at 24 months (P=0.04) and gained 5.7 kg less over the time of the study. There were no significant differences between groups for mean percentage attendance at physical activity sessions (I/C group=24.1%, 95% CI, 15.4-32.9; C/I group=31.7%, 95% CI, 22.4-41.1, P=0.229).\n Children given active intervention followed by body composition monitoring alone reduced their BMI SDS, and fewer children were classified as grossly overweight by the end of the study. If these findings are true, there are important implications for the provision of services managing overweight in the community.", "The duration of untreated psychosis (DUP)-the time from onset of psychotic symptoms to the start of adequate treatment--is consistently correlated with better course and outcome, but the mechanisms are poorly understood.\n To report the effects of reducing DUP on 2-year course and outcome.\n A total of 281 patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment during 4 consecutive years were recruited, of which 231 participated in the 2-year follow-up. A comprehensive early detection (ED) system, based on public information campaigns and low-threshold-psychosis-detecting teams, was introduced in 1 health care area (ED area), but not in a comparable area (no-ED area). Both areas ran equivalent 2-year treatment programs.\n First-episode patients from the ED area had a significantly lower DUP, better clinical status, and milder negative symptoms at the start of treatment. There were no differences in treatment received for the first 2 years between the groups. The difference in negative symptoms was maintained at the 1-year follow-up. There was a statistically significant difference in the Positive and Negative Syndrome Scale negative component, cognitive component, and depressive component in favor of the ED group at the 2-year follow-up. Multiple linear regression analyses gave no indication that these differences were due to confounders.\n Reducing the DUP has effects on the course of symptoms and functioning, including negative symptoms, suggesting secondary prevention of the negative psychopathologies in first-episode schizophrenia.", "To evaluate a model of intensive case management for people with dementia based in a community-based mental health service for older people.\n Quasi-experimental design. Individuals in one community team setting received case management and were compared with those in a similar team without such a service. Forty-three matched pairs were identified. Eligible older people and their carers were interviewed at uptake and again at 6 and 12 months.\n The impact of the scheme upon placement occurred in the second year at the end of which 51% of the experimental group remained at home compared with 33% of the comparison group. For the experimental group significant improvements in the social contacts of older people were noted; a decrease in the stress of their carers was observed, together with a reduction in their input to the care of the client; and there were significant improvements on ratings of overall need reduction, aspects of daily living and level of risk. Differences between the two groups based on service receipt showed higher costs for the experimental group.\n The benefits to older people and their carers confirms previous findings that the most effective case management interventions are those targeted on a highly specific client group. Issues which influence the cost-effectiveness of intensive case management are discussed. The benefits of locating this service within a specialist mental health team are explored in the context of current initiatives to promote greater service integration between health and social services.\n Copyright 2002 John Wiley & Sons, Ltd.", "Adherence to dementia guidelines is poor despite evidence that some guideline recommendations can improve symptoms and delay institutionalization of patients.\n To test the effectiveness of a dementia guideline-based disease management program on quality of care and outcomes for patients with dementia.\n Clinic-level, cluster randomized, controlled trial.\n 3 health care organizations collaborating with 3 community agencies in southern California.\n 18 primary care clinics and 408 patients with dementia age 65 years or older paired with 408 informal caregivers.\n Disease management program led by care managers and provided to 238 patient-caregiver pairs at 9 intervention clinics for more than 12 months.\n Adherence to 23 guideline recommendations (primary outcome) and receipt of community resources and patient and caregiver health and quality-of-care measures (secondary outcomes).\n The mean percentage of per-patient guideline recommendations to which care was adherent was significantly higher in the intervention group than in the usual care group (63.9% vs. 32.9%, respectively; adjusted difference, 30.1% [95% CI, 25.2% to 34.9%]; P < 0.001). Participants who received the intervention had higher care quality on 21 of 23 guidelines (P < or = 0.013 for all), and higher proportions received community agency assistance (P < or = 0.03) than those who received usual care. Patient health-related quality of life, overall quality of patient care, caregiving quality, social support, and level of unmet caregiving assistance needs were better for participants in the intervention group than for those in the usual care group (P < 0.05 for all). Caregiver health-related quality of life did not differ between the 2 groups.\n Participants were well-educated, were predominantly white, had a usual source of care, and were not institutionalized. Generalizability to other patients and geographic regions is unknown. Also, costs of a care management program under fee-for-service reimbursement may impede adoption.\n A dementia guideline-based disease management program led to substantial improvements in quality of care for patients with dementia. Current Controlled Trials identifier: ISRCTN72577751.", "School-based asthma interventions delivered by nonschool staff have been successful but are limited in their reach because of the cost and effort of bringing in outside educators and their inability to establish improved communication about asthma between schools, families, and primary care providers (PCPs). To address these problems, Columbia University and the New York City Department of Education and the New York City Department of Health and Mental Hygiene undertook a randomized controlled trial to test the efficacy of a comprehensive school-based asthma program. In this intervention, school nurses were trained to facilitate the establishment of a preventive network of care for children with asthma by coordinating communications and fostering relationships between families, PCPs, and school personnel. PCPs also received training regarding asthma management. There was limited support for this model. While case detection helped nurses identify additional students with asthma and nurses increased the amount of time spent on asthma-related tasks, PCPs did not change their medical management of asthma. Few improvements in health outcomes were achieved. Relative to controls, 12-months posttest intervention students had a reduction in activity limitations due to asthma (-35% vs -9%, p < .05) and days with symptoms (26% vs 39%, p = .06). The intervention had no impact on the use of urgent health care services, school attendance, or caregiver's quality of life. There were also no improvements at 24-months postintervention. We faced many challenges related to case detection, training, and implementing preventive care activities, which may have hindered our success. We present these challenges, describe how we coped with them, and discuss the lessons we learned.", "Intermediate care (IC) services have been widely introduced in England and have the strategic objectives of reducing hospital and long-term care use. There is uncertainty about the clinical outcomes of these services and whether their strategic aims will be realised.\n A metropolitan city in northern England.\n A quasi-experimental study comparing a group of older people before and after the introduction of an IC service. A quota sampling method was used to match the groups.\n Patients presenting as emergency admissions to two elderly care departments with falls, confusion, incontinence or immobility. Intervention: a city-wide service in which a joint care management team (multi-agency, multi-disciplinary) assessed patient need and purchased support and rehabilitation from sector-based IC teams.\n Nottingham Extended Activities of Daily Living score, Barthel Index, Hospital Anxiety and Depression score, mortality, readmission to hospital, and new institutional care placement at 3, 6 and 12 months post-recruitment.\n There were 800 and 848 patients, respectively, in the control and intervention groups. Clinical outcomes, hospital and long-term care use were similar between the groups. Uptake of IC was lower than anticipated at 29%. An embedded case-control study comparing the 246 patients who received IC with a matched sample from the control group demonstrated similar clinical outcomes but increased hospital bed days used over 12 months (mean +8 days; 95% CI 3.1-13.0).\n This city-wide IC service was associated with similar clinical outcomes but did not achieve its strategic objectives of reducing long-term care and hospital use.", "Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years.\n To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients.\n Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years.\n Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years.\n Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center.\n Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning.\n Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period.\n The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.", "Previous research shows there can be good results from co-financing between welfare sectors on the perceived quality of interprofessional collaboration. However, little is known about the impact on patient outcome of such schemes. This study aimed to assess whether co-financed teams with personnel from primary care, social insurance and social services have any effect on patients' health status. A comparative study of patients attending health care centres with and without a co-financed collaboration model was carried out. Although research has shown positive results from co-financed collaboration on staff and organization, we could not find that this new interdisciplinary team structure gave a better patient health outcome than conventional care.", "To evaluate the effectiveness of anonymised information sharing to prevent injury related to violence.\n Experimental study and time series analysis of a prototype community partnership between the health service, police, and local government partners designed to prevent violence.\n Cardiff, Wales, and 14 comparison cities designated \"most similar\" by the Home Office in England and Wales.\n After a 33 month development period, anonymised data relevant to violence prevention (precise violence location, time, days, and weapons) from patients attending emergency departments in Cardiff and reporting injury from violence were shared over 51 months with police and local authority partners and used to target resources for violence prevention.\n Health service records of hospital admissions related to violence and police records of woundings and less serious assaults in Cardiff and other cities after adjustment for potential confounders.\n Information sharing and use were associated with a substantial and significant reduction in hospital admissions related to violence. In the intervention city (Cardiff) rates fell from seven to five a month per 100,000 population compared with an increase from five to eight in comparison cities (adjusted incidence rate ratio 0.58, 95% confidence interval 0.49 to 0.69). Average rate of woundings recorded by the police changed from 54 to 82 a month per 100,000 population in Cardiff compared with an increase from 54 to 114 in comparison cities (adjusted incidence rate ratio 0.68, 0.61 to 0.75). There was a significant increase in less serious assaults recorded by the police, from 15 to 20 a month per 100,000 population in Cardiff compared with a decrease from 42 to 33 in comparison cities (adjusted incidence rate ratio 1.38, 1.13 to 1.70).\n An information sharing partnership between health services, police, and local government in Cardiff, Wales, altered policing and other strategies to prevent violence based on information collected from patients treated in emergency departments after injury sustained in violence. This intervention led to a significant reduction in violent injury and was associated with an increase in police recording of minor assaults in Cardiff compared with similar cities in England and Wales where this intervention was not implemented.", "This study investigates the impact of a 2-year community intervention on health-related behaviour among adults aged 18-65 years living in deprived neighbourhoods in Eindhoven, The Netherlands. The intervention is evaluated in a community intervention trial with a quasi-experimental design in a longitudinal cohort survey (n=1926 and attrition rate: 31%) using postal questionnaires. In the 2-year implementation phase, more than 40 intervention activities were planned and delivered by intersectoral neighbourhood coalitions. Outcome measures were fruit consumption, vegetable consumption, physical activity, smoking, alcohol consumption and intermediate outcomes of behaviour (i.e. attitudes, self-efficacy, awareness, knowledge and stages of change). The intervention demonstrated no evidence for an impact on vegetable consumption, physical activity, smoking and alcohol consumption and weak evidence for a small impact on (intermediate) outcomes of fruit consumption." ]
"Collaboration between local health and local government is commonly considered best practice. However, the review did not identify any reliable evidence that interagency collaboration, compared to standard services, necessarily leads to health improvement. A few studies identified component benefits but these were not reflected in overall outcome scores and could have resulted from the use of significant additional resources. Although agencies appear enthusiastic about collaboration, difficulties in the primary studies and incomplete implementation of initiatives have prevented the development of a strong evidence base. If these weaknesses are addressed in future studies (for example by providing greater detail on the implementation of programmes; using more robust designs, integrated process evaluations to show how well the partners of the collaboration worked together, and measurement of health outcomes) it could provide a better understanding of what might work and why. It is possible that local collaborative partnerships delivering environmental Interventions may result in health gain but the evidence base for this is very limited. Evaluations of interagency collaborative arrangements face many challenges. The results demonstrate that collaborative community partnerships can be established to deliver interventions but it is important to agree goals, methods of working, monitoring and evaluation before implementation to protect programme fidelity and increase the potential for effectiveness."
"CD005940"
[ "3425252" ]
[ "Prediction of preterm birth." ]
[ "The aim of this study was to assess the value of screening of cervical status in normal as well as in pregnancies with risk factors. 1327 pregnancies were studied prospectively; 16% had a medical history of earlier obstetrical or gynecological complications (group I) and 6% had complications during the first 24 weeks of the current pregnancy (group II). The remainder were considered low-risk pregnancies and randomly divided into groups III and IV. In groups I, II and III cervical scoring in accordance with Westin was performed in weeks 24, 28 and 32. The incidence of births before 37 weeks of gestation was 5.6% in group I, 8.8% in group II, 1.5% in group III and 0.7% in group IV. In presence of the risk factors, 61% of the spontaneous preterm deliveries were predicted early in pregnancy. The predictive value of a normal cervical score was high (about 95%) in all groups. In uncomplicated pregnancies the predictive value of a pathological score was only 4% and for cervical dilatation, 6%. In the risk groups the predictive value of a pathological cervix was 3-5-fold higher. Cervical examination in low-risk pregnancies does not improve prediction of preterms but is a complement in a system for indication for preterm delivery in women with defined risk factors." ]
"We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention."
"CD006273"
[ "12411847", "7893564", "15800328", "15684225" ]
[ "Hypodermoclysis for control of dehydration in terminal-stage cancer.", "The effect of intravenous fluid infusion on blood and urine parameters of hydration and on state of consciousness in terminal cancer patients.", "Effects of parenteral hydration in terminally ill cancer patients: a preliminary study.", "Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies." ]
[ "Many of those involved in palliative care have justifiable objections to the introduction of intravenous hydration in patients with dehydration-associated symptoms and advanced cancer. Researchers from the University of Buenos Aires carried out a randomized, comparative and prospective trail to determine the usefulness of hypodermoclysis in the control of thirst, chronic nausea and delirium. Forty-two patients were randomized into two groups. Both groups received drugs subcutaneously (haloperidol 2.5 mg every 4 hours to control delirium and/or metoclopramide 10 mg every 4 hours to control chronic nausea). The study group also received 1000 ml 5% dextrose in water infusion plus 140 milliequivalent per litre (mEq/L) sodium chloride, at a rate of 42 ml/hour per day. Both groups showed significant and equal improvements in relief of thirst and chronic nausea at 24 hours. After 48 hours, this improvement was maintained in the group that received hydration, but only for the relief of chronic nausea. Delirium did not improve significantly in either group during the 48-hour trial period. Current data suggest that decisions on rehydration of patients with terminal-phase cancer should be based more on the patient's comfort than on providing optimal hydration.", "This prospective study was undertaken to assess the state of hydration in terminal cancer patients with and without intravenous fluids during the last 48 hours of their lives and to correlate various measures of hydration with their state of consciousness. We examined indicators of hydration in the plasma and urine of 68 consecutive patients for whom data were available at 48 hours or less before death. Thirteen of the patients were being treated with intravenous (IV) fluids. Nearly all of the patients studied were found to be dehydrated, as determined by laboratory measurements. State of consciousness correlated inversely with serum sodium (p < 0.001) and urine osmolality (p < 0.02). Patients receiving intravenous fluids were not better hydrated than those without IV therapy, nor was their state of consciousness improved. In light of these findings, which suggest there is no clinical benefit from intravenous infusions, decisions regarding intravenous fluid therapy during the last hours of life should be guided by the preferences of the dying patient and his family.", "Most patients with cancer develop decreased oral intake and dehydration before death. This study aimed to determine the effect of parenteral hydration on overall symptom control in terminally ill cancer patients with dehydration.\n Patients with clinical evidence of mild to moderate dehydration and a liquid oral intake less than 1,000 mL/day were randomly assigned to receive either parenteral hydration with 1,000 mL (treatment group) or placebo with 100 mL normal saline administered over 4 hours for 2 days. Patients were evaluated for target symptoms (hallucinations, myoclonus, fatigue, and sedation), global well-being, and overall benefit.\n Twenty-seven patients randomly assigned to the treatment group had improvement in 53 (73%) of their 73 target symptoms versus 33 (49%) of 67 target symptoms in the placebo group (n=22; P = .005). Fifteen (83%) of 18 and 15 (83%) of 18 patients had improved myoclonus and sedation after hydration versus eight (47%) of 17 and five (33%) of 15 patients after placebo (P = .035 and P = .005, respectively). There were no significant differences of improvement in hallucinations or fatigue between groups. When blinded to treatment, patients (17 [63%] of 77) and investigators (20 [74%] of 27) perceived hydration as effective compared with placebo in nine (41%) of 22 patients (P = .78) and 12 (54%) of 22 investigators (P = .15), respectively. The intensity of pain and swelling at the injection site were not significantly different between groups.\n Parenteral hydration decreased symptoms of dehydration in terminally ill cancer patients who had decreased fluid intake. Hydration was well tolerated, and a placebo effect was observed. Studies with larger samples and a longer follow-up period are justified.", "To explore the association between hydration volume and symptoms during the last 3 weeks of life in terminally ill cancer patients.\n This was a multicenter, prospective, observational study of 226 consecutive terminally ill patients with abdominal malignancies. Primary responsible physicians and nurses evaluated the severity of membranous dehydration (dehydration score calculated from three physical findings), peripheral edema (edema score calculated from seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, hyperactive delirium (Memorial Delirium Assessment Scale), communication capacity (Communication Capacity Scale), agitation (Agitation Distress Scale), myoclonus and bedsores.\n Patients were classified into two groups: the hydration group (n=59) who received 1 l or more of artificial hydration per day, 1 and 3 weeks before death, and the non-hydration group (n=167). The percentage of patients with deterioration in dehydration score in the final 3 weeks was significantly higher in the non-hydration group than the hydration group (35% versus 14%; P=0.002), while the percentages of patients whose symptom scores for edema, ascites and pleural effusion increased were significantly higher in the hydration group than the non-hydration group (44% versus 29%, P=0.039; 29% versus 8.4%, P <0.001; 15% versus 5.4%, P=0.016; respectively). After controlling for multiple covariates and treatment settings, the association between hydration group and dehydration/ascites score was statistically significant. Subgroup analysis of patients with peritoneal metastases identified statistically significant interaction between hydration group and dehydration/pleural effusion score. There were no significant differences in the degree of bronchial secretion, hyperactive delirium, communication capacity, agitation, myoclonus or bedsores.\n Artificial hydration therapy could alleviate membranous dehydration signs, but could worsen peripheral edema, ascites and pleural effusions. It is suggested that the potential benefits of artificial hydration therapy should be balanced with the risk of worsening fluid retention symptoms. Further clinical studies are strongly needed to identify the effects of artificial hydration therapy on overall patient well-being, and an individualized treatment and close monitoring of dehydration and fluid retention symptoms is strongly recommended." ]
"Since the last version of this review no new studies were found. However there is one ongoing, high quality study that has not reached full recruitment. There are insufficient good quality studies to make any recommendations for practice with regard to the use of medically assisted hydration in palliative care patients."
"CD006815"
[ "4605357", "12444816", "9809861" ]
[ "The use of hydroxyzine (Vistaril) in the treatment of anxiety neurosis.", "Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study.", "A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder." ]
[ "nan", "The prevalence of generalized anxiety disorder (GAD) represents an important public health issue. Hydroxyzine, an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients.\n This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score >/= 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo.\n In the intent-to-treat analysis, the mean +/- SD change in HAM-A scores from baseline to endpoint was -12.16 +/- 7.74 for hydroxyzine and -9.64 +/- 7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups.\n Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.", "The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD." ]
"The included studies did not report on all the outcomes that were pre-specified in the protocol for this review. Even though more effective than placebo, due to the high risk of bias of the included studies, the small number of studies and the overall small sample size, it is not possible to recommend hydroxyzine as a reliable first-line treatment in GAD."
"CD002997"
[ "15176685", "8473676", "11520711", "12065339", "10875487", "8430965", "10383596" ]
[ "Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma.", "Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma.", "Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.", "Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin.", "Clarithromycin suppresses bronchial hyperresponsiveness associated with eosinophilic inflammation in patients with asthma.", "A double-blind study of troleandomycin and methylprednisolone in asthmatic subjects who require daily corticosteroids.", "Anti-inflammatory effect of roxithromycin in patients with aspirin-intolerant asthma." ]
[ "A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma. Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d. and salbutamol 200 microg p.r.n. less than twice weekly were studied. Arm A (16 males/six females, aged 48 +/- 16 yrs) received clarithromycin 250 mg b.i.d. for 8 weeks, arm B (eight males/12 females, aged 42 +/- 12 yrs) clarithromycin 250 mg t.id. and arm C (six males/15 females, aged 41 +/- 16 yrs) placebo dextrose tablets. Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20). Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively. Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients. It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma.", "Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma.\n In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone.\n All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group. Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper.\n TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.", "An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.", "To determine the effect of clarithromycin therapy in patients with asthma.\n Randomized, double blind, placebo-controlled trial.\n A tertiary referral center.\n Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community.\n Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks.\n Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo.\n These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.", "Although long-term administration of 14-membered macrolide antibiotics is a therapeutic alternative in asthma, both its pharmacologic mechanism of action and association with the pathogenesis of asthma remain obscure.\n This study investigated the suppressive effect of clarithromycin on airway responsiveness to methacholine provocation testing and examined whether chrarithromycin's antiasthmatic activity is associated with a reduction in eosinophilic inflammation.\n For 8 weeks, patients received 200 mg of clarithromycin or identical-appearing placebo twice daily. We assessed the effects of treatment with clarithromycin on bronchoconstriction precipitated by inhalation of methacholine in 17 adults with mild or moderate bronchial asthma who were in stable clinical condition. A double-blind, randomized, crossover design was used. Eosinophil counts and eosinophilic cationic protein (ECP) levels were determined in blood and sputum samples obtained on the morning of the methacholine provocation testing day.\n After 8 weeks of treatment with clarithromycin, patients' symptoms, blood and sputum eosinophils counts and sputum ECP levels were significantly decreased compared with both placebo and baseline. Furthermore, values of PC20 methacholine improved in all patients after clarithromycin treatment.\n Clarithromycin has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This study suggests interesting therapeutic possibilities for bronchial asthma that warrant further trials.", "A group of 75 subjects with asthma requiring daily corticosteroids for control were enrolled in a 2-yr, double-blind, placebo-controlled study of the use of troleandomycin combined with methylprednisolone, compared with methylprednisolone alone, for the management of their asthma. The primary outcome variables were determination of the lowest stable methylprednisolone dose and assessment of corticosteroid side effects. Methylprednisolone dose was adjusted to maintain optimal control of asthma symptoms. A total of 30 patients receiving TAO and 27 patients receiving placebo completed 1 yr; 17 on TAO and 8 on placebo completed 2 yr of double-blind participation. Control of asthma was equivalent in both groups. The vast majority of patients in both groups achieved alternate-day dosing (29 of 30 on TAO and 23 of 27 on placebo in the first year). The lowest stable doses of methylprednisolone achieved were 10.4 mg/day (placebo) versus 6.3 mg/day (TAO) in the 1-yr group (p = 0.03). However, the baseline dose was also significantly higher in the placebo group (22.8 versus 17.6 mg/day in the TAO group). Therefore, the reductions in methylprednisolone dose were not significantly different between treatment groups. Differences were observed between the two treatment groups in serum IgG, fasting blood sugar, serum cholesterol, and progression of osteoporosis. In each instance the more unfavorable response occurred in those subjects receiving TAO. We conclude that the addition of TAO to methylprednisolone was not accompanied by a reduction in corticosteroid side effects compared with treatment with methylprednisolone alone. Furthermore, no evidence was found for a subset of \"TAO responders.\"(ABSTRACT TRUNCATED AT 250 WORDS)", "Fourteen-membered macrolides, such as roxithromycin, have been reported to exhibit other pharmacological activity including anti-asthmatic effects, besides antibiotic activity.\n This study was designed to investigate the protective effect of roxithromycin on airway responsiveness to the sulpyrine provocation test and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary leucotriene E4 (u-LTE4), a marker of cysteinyl leucotriene overproduction that participates in the pathogenesis of aspirin-intolerant asthma. Also, the present study was designed to examine whether or not its anti-asthmatic activity was associated with a reduction in eosinophilic inflammation.\n For 8 weeks before analysis, subjects received 150 mg of roxithromycin or matching placebo twice daily. We assessed the effects of pretreatment with roxithromycin on bronchoconstriction precipitated by inhalation of sulpyrine in 14 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hyperresponsive to sulpyrine provocation test were allocated to this study. A double-blind, randomized, crossover design was used. Urinary LTE4 was measured by a combined reverse-phase high-performance liquid chromatography (rp-HPLC) enzyme immunoassay on sulpyrine provocation testing day. Blood and sputum samples were taken in the morning on the sulpyrine provocation testing day. Eosinophil counting and measurement of eosinophilic cationic protein (ECP) were performed.\n After the 8 weeks of treatment with roxithromycin, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. On the other hand, values of PC20-sulpyrine did not improve after roxithromycin at all. Furthermore, although challenge with sulpyrine caused a significant increase in u-LTE4, pretreatment with roxithromycin or placebo did not affect excretion of u-LTE4.\n Although roxithromycin does not have antileucotriene effects, it has an antibronchial inflammatory effect associated with eosinophilic infiltration. This study raises further interesting therapeutic possibilities and warrants further trials of new approaches to the treatment of aspirin-intolerant asthma." ]
"Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection."
"CD006358"
[ "12795394", "11758877", "9091670" ]
[ "The effects of a time-limited welfare program on children: the moderating role of parents' risk of welfare dependency.", "Preschool and school age children under welfare reform.", "The effect of monetary incentives and peer support groups on repeat adolescent pregnancies. A randomized trial of the Dollar-a-Day Program." ]
[ "This study examined the effect of a time-limited welfare program on school-age children using data on almost 3,000 children (ages 5-17 at the four year follow up-point) from the random assignment evaluation of Florida's Family Transition Program (FTP). FTP was one of the first welfare reform initiatives to impose a time limit on the receipt of cash assistance, and it combined the time limit with a rich array of mandatory services. The effects of FTP on children were moderated by families' risk of long-term welfare dependency. Contrary to predictions laid out at the outset, there were few effects of FTP on middle childhood and adolescent children for children of parents most likely to be long-term welfare dependent (those most likely to hit the time limit). However, consistent negative effects on this same age group of children were found for children of parents least likely to be long-term welfare dependent--parents who had the largest employment gains--and effects of FTP were most strongly negative for the oldest adolescent children. The findings suggest a different theoretical model for movements into employment than the one suggested in the previous literature for job loss. The findings are discussed in terms of their contribution to research and policy.", "This study compared the behavioral and school problems of young children whose mothers participated in two different income support programs, Jobs First and AFDC. The analyses also included measures of maternal education, maternal health, maternal psychological factors, and family environment. There were no differences in child school or behavioral problems across the income support programs. Children, however, were more likely to have school problems if they were older or if their mothers received less than a high school education, reported child behavioral problems or made criteria for depression on the CIDI. Behavioral problems were more likely to occur if mothers reported violence in the home, many depressive symptoms on the CES-D, few child positive qualities, or if the child had repeated a grade. Several familial factors, then, must be addressed in order to ensure that children excel both academically and behaviorally.", "To test the hypotheses that (1) a monetary incentive promotes peer-support group participation; and (2) peer-support group participation decreases repeat adolescent pregnancies.\n Two-year, prospective, randomized controlled trial.\n Denver, Colo.\n A total of 286 primiparous girls younger than 18 years, whose infants were younger than 5 months.\n Participants were randomized to 4 interventions: monetary incentive and peer-support group, peer-support group only, monetary incentive only, or no intervention.\n Consistency of participation in planned intervention and repeat pregnancy.\n Participation in interventions was generally low. Hypothesis 1 was supported: 58% of those offered a monetary incentive participated in the peer-support groups, compared with 9% of those who were not offered the incentive. Hypothesis 2 was rejected: the peer-support group experience failed to prevent repeat pregnancies. The incidence of second pregnancies at 6 months (9%, 22/248), at 12 months (20%, 49/248), at 18 months (29%, 72/248), and at 24 months (39%, 97/248) following delivery did not vary significantly in relation to intervention strategy. Background sociodemographic characteristics significantly affected the timing of subsequent conceptions but not intervention participation.\n A monetary incentive draws adolescent mothers to sites where they can discuss the costs and benefits of contraception and conception with knowledgeable adults and supportive peers. These discussions do not prevent repeat pregnancies. Further studies are needed to determine if an intervention that produces substantive changes in the daily living environment will eliminate the sexual practices that are responsible for the high rate of repeat pregnancy in this population." ]
"The review set out to examine the potential of financial support to poor families to improve circumstances for children. However, on the basis of current evidence we cannot state unequivocally whether financial benefits delivered as an intervention are effective at improving child health or well-being in the short term. Our conclusions are limited by the fact that most of the studies had small effects on total household income and that, while no conditions were attached to how money was spent, all studies included strict conditions for receipt of payments. We note particular concerns by some authors that sanctions and conditions (such as working hours) placed on families may increase family stress."
"CD003309"
[ "12559133" ]
[ "The effects of the shallow and the deep endotracheal suctioning on oxygen saturation and heart rate in high-risk infants." ]
[ "An experimental study involving repeated-measures within subjects was conducted to examine the effects of shallow and deep endotracheal suctioning (ETS) on the SpO(2) and HR in 27 ventilated high-risks infants. The order in which subjects received the ETS protocol was randomly assigned. The results showed no significant changes in both the SpO(2) and HR responses before, during and after ETS between the two ETS protocols. It is concluded that when there is no beneficial effect of performing deep ETS, it should not be carried out due to the potential hazard of direct irritation with more negative pressure on the airways in high-risk infants." ]
"There is no evidence from randomised controlled trials concerning the benefits or risks of deep versus shallow suctioning of endotracheal tubes in ventilated neonates and infants. Further high quality research is required."
"CD002309"
[ "17573446", "19716960", "17463412", "19716961", "11498212", "16099292" ]
[ "Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD.", "Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials.", "Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease.", "Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials.", "Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study.", "Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial." ]
[ "Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD.\n In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 61.0 (12.6)% predicted) received 500 microg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly.\n Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV(1) improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018).\n PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV(1).", "The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD.\n In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 microg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV(1)) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov, number NCT00297102 for M2-124, and NCT00297115 for M2-125.\n Patients were assigned to treatment, stratified according to smoking status and treatment with longacting beta(2) agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV(1) increased by 48 mL with roflumilast compared with placebo (p<0.0001). The rate of exacerbations that were moderate or severe per patient per year was 1.14 with roflumilast and 1.37 with placebo (reduction 17% [95% CI 8-25], p<0.0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was -2.17 kg.\n Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies.\n Nycomed.", "The oral phosphodiesterase-4 (PDE4) inhibitor, roflumilast, can improve lung function in moderate chronic obstructive pulmonary disease (COPD). Whether treatment is effective in more severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) over a longer period is unknown.\n To determine whether roflumilast improves lung function and decreases exacerbation frequency over 1 year in patients with stable COPD.\n We conducted a randomized, placebo-controlled, double-blind, parallel-group trial for 1 year. We recruited 1,513 patients (mean post-bronchodilator FEV1 41% predicted), 760 receiving oral 500 microg roflumilast and 753 receiving placebo once daily.\n We recorded post-bronchodilator FEV1, exacerbation rate, St. George's Respiratory Questionnaire total score at the study end point, and number and type of reported adverse events during treatment. Post-bronchodilator FEV1 increased by 39 ml with roflumilast compared with placebo by 52 weeks (p=0.001). The mean exacerbation rate was low and comparable in both treatment groups (0.86 vs. 0.92 exacerbations/patient/yr for roflumilast and placebo, respectively). In a retrospective analysis, the exacerbation rate in patients in GOLD stage IV disease was 36% lower in patients treated with roflumilast than in those treated with placebo (1.01 vs. 1.59 exacerbations/patient/year, respectively; p=0.024). The St. George's Respiratory Questionnaire total score did not differ between treatments. The commonest adverse events related to roflumilast treatment were diarrhea, nausea, and headache, which usually subsided during continued treatment. However, roflumilast resulted in more withdrawals within the first 3 to 4 weeks of administration.\n In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate or health status. However, patients with very severe disease experienced fewer exacerbations with roflumilast.", "Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated.\n In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 microg or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1 s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128.\n In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal.\n Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients.\n Nycomed.", "Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disease that causes great morbidity and mortality despite treatment. There is evidence for airway inflammation in COPD. Cilomilast is an orally active, potent, selective phosphodiesterase type 4 inhibitor, which in vitro can affect cells thought to be of clinical importance in COPD. Our aim was to assess the safety, efficacy, and dose response of cilomilast in the treatment of patients with this disease.\n We did a 6-week, randomised, dose-ranging study in 424 patients with COPD (forced expiratory volume in 1 s [FEV(1)] 46.8% of predicted, FEV(1)/forced vital capacity [FVC] 54.6%, and postsalbutamol reversibility 5.4%). We randomly assigned individuals at 60 European centres to receive cilomilast 5 (n=109), 10 (n=102), or 15 (n=107) mg twice daily, or placebo (n=106). The main outcome measure was trough FEV(1) before and after use of a bronchodilator. Analyses were by intention to treat.\n Cilomilast 15 mg twice daily significantly improved FEV(1) compared with placebo (mean 130 mL vs -30 mL [95% CI 90-240] at week 6, p<0.0001). FVC and peak expiratory flow were also improved (p=0.001 and p<0.0001, respectively). Quality of life measures did not differ significantly between the groups. There were no significant differences in serious adverse events between the groups.\n Cilomilast 15 mg twice daily might be an effective maintenance treatment for COPD. Further clinical studies are underway.", "Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD.\n This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 microg (n=576), roflumilast 500 microg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat.\n 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 microg group, and 124 (22%) from the roflumilast 500 microg group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 microg (by 74 mL [SD 18]) and roflumilast 500 microg (by 97 mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 microg (-3.4 units [0.6]) and roflumilast 500 microg (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 microg, and roflumilast 500 microg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study.\n Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life." ]
"In people with COPD, PDE4 inhibitors offered benefit over placebo in improving lung function and reducing likelihood of exacerbations, however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common. The optimum place of PDE4 inhibitors in COPD management remains to be defined. Longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, healthcare utilisation or mortality in COPD."
"CD001991"
[ "6734291", "21714641", "5345935", "1991274", "3711252", "2776873" ]
[ "Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York.", "Reduced lung-cancer mortality with low-dose computed tomographic screening.", "Earlier diagnosis and survival in lung cancer.", "Screening for lung cancer. A critique of the Mayo Lung Project.", "Multiphasic Health Checkup Evaluation: a 16-year follow-up.", "A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR." ]
[ "The Memorial Sloan-Kettering lung cancer screening program was begun in 1974 to evaluate sputum cytology as a supplement to the annual chest x-ray examination for early detection and diagnosis. The 10,040 adult, male cigarette smokers who enrolled were randomly assigned to receive annual chest x-ray examinations only or a dual screen with annual chest x-ray examination and four monthly sputum cytology evaluation. Over 40 percent of the 288 who developed lung cancer were diagnosed in stage I, and their survival was 76 percent at five years; overall survival was 35 percent. Nearly one third of the lung cancers detected on first examination on the dual screen, and 14 percent of those on subsequent examinations were found by cytologic examination. The same number of cancers developed in the x-ray screen only group, and were diagnosed at a later date. Despite the delay, survival and mortality were the same, suggesting that the squamous carcinomas detected by cytologic examination alone are very slow growing and tend to remain localized until detectable by x-ray examination.", "The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.\n From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.\n The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02).\n Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).", "In a controlled investigation the survival prospects of lung cancer in a population of men aged 40 and over who had been offered six-monthly chest radiographs over a period of three years were compared with lung cancer in a similar population without such x-ray facilities. The five-year survival rate of lung cancer in the study series was 15%, and in cases discovered by six-monthly examination 23%, compared with 6% in the control series. The average expectation of life after diagnosis was 2.5 years for the test cases and 1.2 for the control cases. Survival declined with age. Of resected lung cancer, 32% survived five years in the test series and 23% in the control series. The five-year survival rate for squamous carcinoma and adenocarcinoma in the test series was 28% and 25% respectively, compared with 15% and nil in the control series.On the basis of these results it is concluded that through earlier radiological detection a modest improvement in the prognosis of lung cancer can be achieved.", "The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.", "The Multiphasic Health Checkup Evaluation Study, a long-term clinical trial, has been completed. A study group of 5156 men and women age 35-54 at entry was urged to have annual multiphasic health checkups (MHCs) for 16 years. A control group of 5557 comparable subjects was not so urged but was followed up in a comparable fashion. The mean and median number of MHCs per person were 6.8 and 6, respectively, in the study group and 2.8 and 1, respectively, in the control group. During 16 years the study group experienced a 30% reduction (p less than 0.05) in deaths from pre-specified \"potentially postponable\" causes, largely associated with lower death rates from colorectal cancer and hypertension. This reduction was most pronounced in the early years of the study. The two groups did not differ to a statistically significant degree in mortality from all other causes (84% of total mortality) or in total mortality. There was no difference in self-reported disability in the overall groups. In the setting of our prepaid health care plan where MHCs were already available on a voluntary basis, a program of urging middle-aged persons to undergo regular MHCs brought about a substantial reduction in mortality from preselected diseases.", "A prospective and controlled study for early detection of lung cancer in the county of Erfurt with a follow-up of 10 years is presented. A collective of 41,532 males born between 1907 and 1932 was screened by chest fluorography at 6 month intervals and compared with a control group consisting of 102,348 males of the same age, who were screened at intervals of about 18 months. No significant reduction of overall mortality and of lung cancer mortality was achieved. Semi-annual screening brought about a higher detection rate (9%/6.5%), an increase in the resection rate (28%/19%) and higher 5 and 10 year survival rates (52%; 27%/39%; 19%) of resected patients than screening in 18 month intervals. Among those patients who refused resection or were surgically untreatable, the difference in survival rates between the two investigation groups lasted only up to the 12 months barrier. This is regarded as the effect of the lead-time bias. Fluorographic screening is effective only in patients with peripheral cancers. Patients resected for central lung cancers did not show differences in the survival rates. In both investigation groups considered together surgical therapy was possible mainly in those patients who had been detected by screening (resection rate: 48%; 5 yr survival rate: 26.9%). The resection rate of all the others amounted to 9%, the 5 yr survival rate to 1.4%. Therefore we consider fluorography to time as the only chance for lung cancer control of high risk groups in spite of the absence of reduction of lung cancer mortality." ]
"The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Annual low-dose CT screening is associated with a reduction in lung cancer mortality in high-risk smokers but further data are required on the cost effectiveness of screening and the relative harms and benefits of screening across a range of different risk groups and settings."
"CD003144"
[ "7006425", "3896372", "6375991", "2064291" ]
[ "Randomized prospective evaluation of the EEA stapler for colorectal anastomoses.", "Staples or sutures for low colorectal anastomoses: a prospective randomized trial.", "[Technic of rectum anastomoses in rectum resection. A controlled study: instrumental suture versus hand suture].", "[The best anastomoses after colonic resection]." ]
[ "A randomized, prospective study should be done to evaluate any new procedure or instrument. Our experience with the end-to-end anastomosis (EEA) stapler suggests that an anastomosis can be created in a shorter time than is required for the traditional hand-sewn technique. This difference is even greater when the anastomosis is technically difficult and located deep within the pelvis. There appears to be little difference in the security of a hand-sewn anastomosis compared with that of stapled anastomosis. Postoperative complications appear similar. With the stapler, however, there is an increased risk of intraoperative complications that are not apparent with the traditional hand-sewn technique. These include rectal tears and anastomotic defects. It appears that the EEA stapler can save as many as 12 percent of rectums that otherwise might have to be removed because of technical inability to perform an anastomosis.", "One hundred and eighteen patients undergoing low colorectal anastomoses were randomly allocated to reconstitution by either single layer interrupted extramucosal sutures or circular staple gun. In the 60 patients undergoing sutured anastomosis there were 2 (3 per cent) clinical leaks and 4 (7 per cent) radiological leaks, and no failures. Of the 58 patients who underwent stapled anastomosis there were 4 failures, 7 (12 per cent) clinical leaks, 14 (24 per cent) radiological leaks and 1 death. Stapled anastomoses were more than ten times as expensive as sutured anastomoses and there were no savings in time or numbers of associated colostomies. An interrupted extramucosal suture technique remains the ultimate standard for low colorectal anastomosis.", "Stapler and manual sutures in rectal end-to-end anastomoses were compared in a controlled trial. The following results were obtained: For the analysis the cases naturally separated into three groups, A (manual suture), B (planned stapler suture) and WD (\"withdrawn\" cases, from both groups, in which continence could be maintained only with a stapler suture). The distribution of the WD cases in dependence on localization and sex varied significantly from groups A and B, while A and B remained comparable, in spite of the WD cases. The analysis of the date showed no, or only slight, clinical differences. In a comparison of the two stapler groups B and WD, significantly more suture dehiscences, colocutaneous fistulae and post-operative disturbances in bladder function were found in group WD. As a general conclusion we can state that: In comparable anastomosis localizations it is possible to achieve almost the same clinical results with both suture techniques. With a circular stapler it is, however, technically possible to perform rectum resections in cases in which this was not previously possible, particularly in men with a narrow pelvis and a stale pelvic floor. To what extent this still is an advantage after the local recurrences are taken into consideration remains to be seen.", "Among the numerous anastomotic techniques after colonic resection, the mechanical sutures using staplers have been credited with a lower incidence of anastomotic leakage than hand-sewn anastomoses. This hypothesis has been tested in two multicentre, prospective, randomized trials after right hemicolectomy for carcinoma and after left colectomy with colorectal anastomosis. After right hemicolectomy, the stapled anastomosis using the GIA and TA staplers appeared to be superior to all hand-sewn anastomoses. This superiority was not apparent after left colectomy followed by colorectal anastomosis. Although the leakage rate of stapled anastomoses was similar to hand-sewn anastomoses, they carry a high rate of intra-operative mishaps. Furthermore, the stapler does not permit a lower anastomosis in this study. Finally, the overall cost of a stapled anastomosis is superior to the cost of an hand-sewn anastomosis." ]
"The evidence found was insufficient to demonstrate any superiority of stapled over handsewn techniques in colorectal anastomosis surgery, regardless of the level of anastomosis. There were no randomised clinical trials comparing these two types of anastomosis in elective conditions in the last decade. The relevance of this research question has possibly lost its strength where elective surgery is concerned. However, in risk situations, such as emergency surgery, trauma and inflammatory bowel disease, new clinical trials are needed."
"CD004654"
[ "9802740", "11092289", "12797714", "11483229", "10868832", "15161773", "15660732", "12757988", "10333912", "12351462", "12832314", "10631622", "12213867" ]
[ "A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.", "Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.", "The effect of prandial glucose regulation with repaglinide on treatment satisfaction, wellbeing and health status in patients with pharmacotherapy naïve Type 2 diabetes: a placebo-controlled, multicentre study.", "Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes.", "Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.", "Repaglinide versus nateglinide monotherapy: a randomized, multicenter study.", "Effects of nateglinide on myocardial microvascular reactivity in Type 2 diabetes mellitus--a randomized study using positron emission tomography.", "Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin.", "Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.", "Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy.", "Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.", "Repaglinide in type 2 diabetes: a 24-week, fixed-dose efficacy and safety study.", "Efficacy and safety of nateglinide in type 2 diabetic patients with modest fasting hyperglycemia." ]
[ "The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes.\n This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded.\n From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated.\n This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.", "To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions.\n In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.\n At study end point, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 0.0001 vs. metformin and placebo). All regimens were well tolerated.\n Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA1c, FPG, and postprandial hyperglycemia.", "This prospective, 16-week, randomised, double-blind, parallel-group study assessed the differential impact of the prandial glucose regulating oral hypoglycaemic drug, repaglinide, and placebo upon perceptions of quality of life (QoL) and treatment satisfaction in pharmacotherapy-naive patients with Type 2 diabetes. In addition, the study assessed whether these outcomes were influenced by the patients' level of glycaemic control. A total of 253 patients were randomised in a 2:1 ratio of repaglinide: placebo, with doses taken flexibly with main meals (2-4 per day), whenever they were eaten. Repaglinide was initiated at 0.5 mg per meal, increased to 1 mg after 4 weeks if fasting plasma glucose exceeded 7.8 mmol/l. QoL and treatment satisfaction outcomes were compared using generic and disease-specific self-assessment measures, previously applied in diabetes: the WHO Wellbeing Questionnaire (WHO-WBQ), WHO Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ) and EuroQoL EQ-5D. Over the trial period, repaglinide-treated patients reported a significant 9% improvement in (WHO-DTSQ) treatment satisfaction score (p < 0.05). No significant increase was associated with placebo. The correlation between decrease in glycated haemoglobin (HbA1c) and increase in treatment satisfaction (WHO-DTSQ) was -0.22 (p < 0.01). Scores obtained with the other measures did not change significantly during the trial in either group, but the cohort exhibited only a slight reduction in wellbeing (WHO-WBQ) and health status (EQ-5D) at baseline compared with the background population. In conclusion, flexible mealtime dosing with oral medication appears to be well accepted by pharmacotherapy-naïve patients with Type 2 diabetes. The results suggest that repaglinide provides a higher level of treatment satisfaction than placebo, and this may in part relate to improved glycaemic control.", "The prandial glucose regulator repaglinide has a rapid onset of action, a short half-life and is metabolised mainly by the liver. Here we report the findings of a 10-week, double-blind, parallel, placebo controlled, randomised trial with repaglinide in 25 diet-treated, sulphonylurea-naïve patients with Type 2 diabetes. Repaglinide was titrated, based on capillary blood glucose, from 0.5 mg to a maximum of 4 mg, preprandially with breakfast and dinner. After 10 weeks, repaglinide was associated with a decrease in HbA(1c) of 2.3%Hb relative to the placebo group (P=0.018). This reflected a 30% decrease within the repaglinide group from a mean HbA(1c) of 7.0 to 4.9%Hb (P<0.002). Repaglinide was also associated with a decrease in fructosamine, by 0.88 mmol/l, relative to placebo (P<0.001), with a 20% decrease (from 3.80 to 3.04 mmol/l) within the repaglinide group (P<0.001). Fasting and postprandial blood glucose concentrations decreased in association with repaglinide by 3.6 and 6.4 mmol/l, respectively, relative to placebo (P<0.001 in each case). Within the repaglinide group fasting and postprandial blood glucose decreased by 3.9 and 6.2 mmol/l, respectively (P<0.001 in each case). The number of patients reporting hypoglycaemia in the repaglinide group was similar to placebo (15 vs. 20, respectively; NS). Test meal assessments confirmed that repaglinide effectively controls glucose levels by stimulating mealtime insulin secretion. Fasting serum insulin concentration was not raised compared to baseline or placebo during repaglinide therapy, albeit that fasting glucose levels were decreased by repaglinide. Twice-daily meal-related insulin secretagogue therapy with repaglinide, a new short and rapid-acting prandial glucose regulator, is capable of improving all measures of glycaemic control without increased hypoglycaemia or fasting hyperinsulinaemia.", "The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state.\n This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN). Adverse events and hypoglycemic episodes were recorded.\n After a liquid meal challenge, nateglinide rapidly increased mealtime insulin levels within 30 min of drug intake and reduced mealtime glucose excursions without affecting triglyceride levels. At study end point, reduction of HbA1c levels was statistically significantly greater with nateglinide at doses of 60, 120, and 180 mg than placebo (-0.45, -0.62, and -0.64%, respectively; P<0.05). The mean level of FPG was significantly reduced versus placebo in the nateglinide 120-mg group only (-1.14 mmol/l P<0.01). Overall, nateglinide was well tolerated.\n This study demonstrated that nateglinide improves mealtime and mean glycemic control in a dose-dependent manner by restoring early insulin secretion phase. Nateglinide was well tolerated and is suitable for the treatment of patients with type 2 diabetes.", "A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise.\n Enrolled patients (n = 150) had received treatment with diet and exercise in the previous 3 months with HbA(1c) >7 and < or =12%. Patients were randomized to receive monotherapy with repaglinide (n = 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA(1c) and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia.\n Mean baseline HbA(1c) values were similar in both groups (8.9%). Final HbA(1c) values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA(1c) were significantly greater for repaglinide monotherapy than nateglinide monotherapy (-1.57 vs. -1.04%; P = 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (-57 vs. -18 mg/dl; P < 0.001). HbA(1c) values <7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group.\n In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA(1c) and FPG values after 16 weeks of therapy.", "To evaluate effects of the oral antidiabetic insulinotropic agent nateglinide on myocardial blood flow (MBF) and microvascular reactivity in Type 2 diabetic patients.\n Forty-seven Type 2 diabetic patients were randomly assigned 2 : 1 to nateglinide 120 mg (t.i.d., n = 33) or placebo (n = 14). At baseline and after 16 weeks of treatment, MBF was quantified using positron emission tomography with N-13 ammonia at rest, during endothelial-dependent stimulation by cold pressor test and during adenosine-mediated vasodilation. Additional blood samples were taken to assess glycaemic control and lipid profile.\n MBF at rest and during adenosine did not change during the study. The percentage of flow increase from rest during cold pressor test did not improve significantly in the nateglinide group vs. placebo (from 26.1 +/- 37.2% to 29.1 +/- 27.8% between week 0 to week 16 for nateglinide vs. 14.9 +/- 37.1% to 18.1 +/- 28.4% for placebo; P = 0.07 for nateglinide when adjusted for higher baseline values). Nateglinide decreased HbA1c by 0.4% (from 7.6 +/- 0.9% to 7.2 +/- 1.3%) compared to an increase of 0.5% in the placebo group (from 7.9 +/- 0.8% to 8.4 +/- 1.7%; P = 0.02 for nateglinide). No differences between the two groups were observed in insulin levels and lipid status.\n Nateglinide neither improved, nor impaired myocardial blood flow in Type 2 diabetic patients. Potential effects on endothelial-dependent myocardial blood flow remain to be investigated further. Positron emission tomography is a sensitive approach to assess the effects of therapeutic agents on myocardial blood flow in patients with diabetes.", "To compare glycaemic control and cardiovascular risk profile in patients with type 2 diabetes following 12 months' treatment with either repaglinide or metformin.\n This was an open uncontrolled randomised study in n=112 patients with inadequately controlled type 2 diabetes not previously treated with oral hypoglycaemic agents. Patients beginning treatment with either repaglinide or metformin entered an 8-week titration period (to optimise dosage: repaglinide, 2-4 mg/day; metformin, 1500-2500 mg/day) followed by a 12-month treatment period. Glycaemic control and cardiovascular risk factors were determined at baseline and at the end of the treatment period.\n Mean (S.D.) final drug doses were 3 (+/-1) mg/day in the repaglinide group and 2000 (+/-500) mg/day in the metformin group. Significant improvements in glycaemic control [glycated haemoglobin, fasting and 2-h postprandial plasma glucose (PPG)] were demonstrated in both treatment groups. The decrease in PPG was significantly greater in the repaglinide group (P<0.05). During the treatment period, fasting plasma insulin (FPI) decreased significantly in both groups, more so with metformin (P<0.05). Two-hour postprandial plasma insulin (PPI) levels decreased only in the metformin group (P<0.05). Significant improvements between baseline and final visit were demonstrated in one or both groups in the following cardiovascular risk factors: total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, plasminogen activator inhibitor, lipoprotein(a) and homocysteine. No changes were observed in high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I, apolipoprotein B, fibrinogen, body mass index (BMI) or blood pressure.\n The use of repaglinide or metformin in drug therapy-nai;ve patients with type 2 diabetes over a 12-month period is associated with improvements in both glycaemic control and cardiovascular risk profile. The latter cannot necessarily be attributed to the pharmacotherapy per se, but provides reassurance in the context of initiating oral hypoglycaemic drug therapy with these agents.", "To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes.\n A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period.\n In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05).\n Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.", "To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes.\n A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l.\n Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide.\n Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.", "An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.\n Enrolled patients (n = 192) had HbA(1c) >7% and < or =12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide < or =2.5 mg, metformin < or =500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.\n Final HbA(1c) values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA(1c) (-1.28 vs. -0.67%; P < 0.001) and of fasting plasma glucose (FPG) (-39 vs. -21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 A.M. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.\n The addition of repaglinide to metformin therapy resulted in reductions of HbA(1c) and FPG values that were significantly greater than the reductions observed for addition of nateglinide.", "In this 24-week multicenter, double-blind, randomized, fixed-dose trial, 361 patients having type 2 diabetes received daily preprandial treatment with placebo (n = 75), repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146). By a last-observation carried-forward calculation, repaglinide 1 mg or 4 mg treatment decreased mean fasting plasma glucose (FPG) values (by -47 mg/dL or -49 mg/dL) while the placebo group had increased FPG values (by 19 mg/dL). For the repaglinide treatment groups at the end of the study, changes in HbA1c from baseline values ranged from 1.8 to 1.9 percentage points lower than the placebo group. There were no events of severe hypoglycemia. Nearly all hypoglycemic symptom episodes had blood glucose levels above 45 mg/dL. Repaglinide was well tolerated in a preprandial fixed-dose regimen of 1 mg or 4 mg, assigned without adjustment for clinical parameters.", "Nateglinide is a fast-acting insulin secretion agent that specifically targets postprandial hyperglycemia in patients with type 2 diabetes. The recent reduction in the diagnostic criteria for diabetes and improved understanding of the importance of early insulin secretion served as the rationale for this multicenter, double-blind, randomized, parallel-group, 24-wk study performed in 675 patients with type 2 diabetes but only moderately elevated fasting plasma glucose (FPG) (FPG = 7.0-8.3 mmol/liter) to assess the efficacy and safety of three fixed doses of nateglinide (30, 60, or 120 mg, with meals). A substudy of the effects on early insulin release and prandial glucose excursions following a standardized breakfast was performed in 127 subjects. Nateglinide was well tolerated and elicited a dose-dependent reduction of placebo-adjusted hemoglobin A(1c) (Delta = -0.26 to -0.39%) and FPG (Delta = -0.51 to -0.73 mmol/liter) accompanied by a dose-related increase in suspected hypoglycemic episodes. However, confirmed hypoglycemia occurred in only 5.3% of patients treated with the highest dose, compared with 1.2% in placebo-treated patients (P < 0.05). Nateglinide increased early insulin release and reduced prandial glucose excursions (P < 0.05 vs. placebo). In sum, nateglinide is a safe and effective therapeutic option for treatment of patients with mild to moderate fasting hyperglycemia." ]
"Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin, and may be indicated where side effects of metformin are intolerable or where metformin is contraindicated. However, there is no evidence available to indicate what effect meglitinides will have on important long-term outcomes, particularly mortality."
"CD009138"
[ "6386793", "1924659", "1546154", "6211994", "2649156", "7003429", "2858187", "7044154", "8297924", "7592505", "3927356", "2201481", "4923928", "9413414", "7868849", "108739", "7873952", "7156248", "6371879", "2236455", "7231652", "3133710", "6225150", "8471679", "2258378", "7306613", "2941771", "6406443", "6431461", "2963054", "3283804", "538213", "3157576", "1666199" ]
[ "A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.", "A controlled study of mianserin in moderately to severely depressed outpatients.", "A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study.", "Controlled trial of zimelidine, a 5-HT reuptake inhibitor, for treatment of depression.", "Verapamil in affective disorders: a controlled, double-blind study.", "Comparative effects of phenelzine and amitriptyline: a placebo controlled trial.", "Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.", "Trazodone in depressed outpatients.", "Thyroid functioning during treatment for depression.", "A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.", "Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study.", "Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel-group comparison against amitriptyline and placebo.", "Controlled trial of amitriptyline in general practice.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients.", "A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness.", "Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.", "The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo.", "A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder.", "Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.", "Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo.", "Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients.", "A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder.", "A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant.", "Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.", "Neuropsychological assessment and EEG sleep in affective disorders.", "A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression.", "Antidepressant response and plasma concentrations of bupropion.", "Amoxapine and amitriptyline. I. Relative speed of antidepressant action.", "Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial.", "Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression.", "Changes in weight during treatment for depression.", "High incidence of multisystemic reactions to zimeldine.", "Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia." ]
[ "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.", "In a 7-week prospective multicentre study, the efficacy, tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n = 173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy ('very good' or 'good' response: moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline, but there was no significant difference between moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the moclobemide or placebo groups. In conclusion, both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while moclobemide had fewer side effects.", "The authors conducted a double-blind, placebo-controlled clinical trial of the selective 5-HT reuptake inhibitor zimelidine in the treatment of major depressive illness. Zimelidine had the same antidepressant efficacy as amitriptyline but significantly fewer side effects, especially anticholinergic effects.", "Eighty-six depressed inpatients were divided into four groups: patients in each of three groups were treated, respectively, with identical capsules of verapamil, amitriptyline, or placebo, whereas the fourth group was treated eclectically by the ward physician with so-called state-adjusted treatment (SAT). Each treatment period lasted 5 weeks. Psychopathology was assessed with the Hamilton Rating Scale for Depression, by the Zung self-rating scale, by the 100-mm analog scale, and by general clinical impression. Results indicated that amitriptyline and SAT were superior to verapamil or placebo. There was no significant difference between verapamil and placebo or between SAT and amitriptyline. This finding was more definitive in the homogeneous subgroup of 55 women with DSM-III diagnosis of Major depression. In addition, 12 manic inpatients (DSM-III) were treated orally with verapamil, 24 with neuroleptics, and 11 with both neuroleptics and lithium carbonate. The decline of their psychopathology, assessed by the Brief Psychiatric Rating Scale (BPRS) and general impression, was fully comparable. Using Analysis of Variance (ANOVA), the statistical difference among courses of psychopathology expressed as total BPRS scores reaches borderline significance in favor of verapamil. In contrast to neuroleptics, verapamil did not induce any sedative, hypnotic, or cataleptic effects, and was well tolerated.", "nan", "Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam.", "The authors compared the nontricyclic antidepressant trazodone with amitriptyline and placebo in a double-blind study of 202 unipolar depressed outpatients. Trazodone's clinical efficacy was similar to that of amitriptyline, with both active drugs producing significantly more clinical improvement than placebo. The incidence of anticholinergic side effects was lower for the patients taking trazodone than for those taking amitriptyline.", "Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a double blind study with either moclobemide, placebo or amitriptyline, for 42 days. The psychopathological assessment and HRSD were done on seven day intervals and thyroid analysis was done on 14 day intervals. At the end of therapy, the levels of T4 and fT4 decreased significantly in the responders if amitriptyline was used, and non-significantly if placebo or moclobemide were used. The T4 and fT4 values of the non-responders increased non-significantly. The weight change was minimal and non-significant.", "A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.\n One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.\n At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.\n In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety.", "3-Cyano-imipramine (cianopramine) is a potent and selective inhibitor of serotonin uptake into synaptosomes. In a double-blind trial, 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine (n = 20, mean daily dose 3.3 +/- 0.6 mg) amitriptyline (n = 20, mean daily dose 86.4 +/- 21 mg) or placebo (n = 20) orally. According to the ratings of the Hamilton Scale of Depression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P less than 0.02). The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group. The findings suggest that cianopramine is a promising new antidepressant.", "In a double-blind, random-assignment, parallel-group trial, outpatients with major depression received either the new antidepressant clovoxamine, the tricyclic amitriptyline, or placebo for 6 weeks. By an \"improvement\" criterion of 50% or greater improvement in the Hamilton Depression Scale (HAM-D) total score, 88% of clovoxamine completers improved versus 75% with amitriptyline and 43% with placebo; however, due to small numbers, the differences failed to reach statistical significance. Diminished salivary flow was significantly greater with amitriptyline, as were complaints of dry mouth, somnolence, dizziness, and headache. Nausea and vomiting were more common in the clovoxamine-treated group. With amitriptyline, but not with clovoxamine, memory performance declined over a month. However, psychomotor performance was not affected.", "A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments.", "This study was designed to compare the efficacy, safety, tolerability profiles, and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression.\n Outpatients with DSM-III-R major depression were randomly assigned to double-blind treatment for 8 weeks with sertraline (50-200 mg daily), amitriptyline (50-150 mg daily), or matching placebo. Assessments included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness scale, Clinical Global Impressions-Improvement scale, Global Assessment Scale, Profile of Mood States, Beck Depression Inventory, Quality of Life Enjoyment and Satisfaction Questionnaire, and Health-Related Quality of Life battery.\n All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter. The antidepressant effects of amitriptyline and sertraline were significantly (p < .05) greater than placebo and did not differ significantly from each other. Sertraline was associated with significantly (p < .05) greater subjective (i.e., patient-rated) improvement in mood than amitriptyline or placebo. Both active drugs were associated with greater improvements than placebo on most quality of life measurements. On several items, sertraline, but not amitriptyline, was superior to placebo. There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales. Amitriptyline therapy was associated with significantly more treatment-related adverse events, and discontinuations due to treatment-related adverse events, in comparison to both sertraline and placebo therapy.\n Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales. These results show that sertraline therapy is better tolerated than amitriptyline therapy. Quality of life was also improved by effective antidepressant treatment, with sertraline showing a tendency to produce greater improvements on quality of life measures.", "We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized to mianserin (n = 50), amitriptyline (n = 50) or placebo (n = 49). Medication was taken in a nightly (qhs) dose. During Week 1, the maximum dose was 60 mg mianserin, 120 mg amitriptyline or two placebo capsules. Beginning at Day 7 (through Day 42) maximum dosages were 150 mg mianserin, 300 mg amitriptyline or five placebo capsules. At multiple weeks and endpoint, statistically significant reductions in the Hamilton Depression Scale (HAM-D) 17- and 21-item scores were recorded for both active drugs compared with placebo. Positive results with the HAM-D were corroborated by other measures of efficacy. There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy; however, the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline, in terms of percentage of patients showing > or = 50% improvement at Weeks 2 (30% vs 23%) and 4 (61% vs 44%). The most common adverse experiences were somnolence (amitriptyline and mianserin 60%, placebo 31%) and dry mouth (amitriptyline 76%, mianserin 30% and placebo 20%). Our results indicate that mianserin is clearly superior to placebo, compares favorably with amitriptyline, and is a safe, well-tolerated, effective medication in the treatment of depressed outpatients.", "In a multicenter, placebo-controlled, clinical trial, the efficacy of Limbitrol was compared with that of its components, amitriptyline and chlordiazepoxide. All patients had a diagnosis of primary depression. Data from 279 patients were evaluated using the Hamilton depression scale, the Beck depression inventory, and physician and patient global change measures. Statistically significant differences favoring Limbitrol occurred after 1 week of treatment, and a trend in favor of Limbitrol continued throughout the remaining 3 weeks. In most efficacy comparisons, the combination was as good as, or better than, amitriptyline alone. It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment. Each component produced an independent contribution to the total therapeutic effect: the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks. A trend favoring amitriptyline over chlordiazepoxide was evident by week 4. The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups. Limbitrol-treated patients exhibited more sedation, but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects.", "To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients.\n Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks.\n Primary care in Oxfordshire.\n 91 patients in primary care who had major depression.\n Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks.\n At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours.\n As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.", "One hundred and fifteen patients from 5 general practices participated in a 12-week, double-blind study comparing L-tryptophan, amitriptyline, L-tryptophan-amitriptyline combination and placebo in the treatment of depression. Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo. Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups. Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups, but this difference was not significant. Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups. Standard haematological and biochemical profiles did not alter significantly in any group, but mean heart rate was significantly increased in patients receiving amitriptyline. There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms.", "The cardiovascular effects of trazodone ( TZD ), amitriptyline (AMT) and placebo were studied in out-patients with major depression. AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties. TZD , in contrast, had no quinidine-like effects and minor effects on systolic time intervals. However, it was not without any cardiovascular effects. Although TZD was shown to be a safer preparation than the reference drug AMT, long-term monitoring is needed to explain the minor effect on heart rate and T wave changes.", "Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.", "This report examines the hypothesis that for phenelzine to be more effective than placebo it is necessary to achieve at least 80% inhibition of platelet MAO activity. This hypothesis was examined in the context of a double-blind comparison of phenelzine, amitriptyline and placebo in depressed patients. When phenelzine became significantly more effective than placebo at 4 weeks, the average MAO inhibition was 85%. By the 5th week, with MAO inhibition greater than 90%, phenelzine was significantly more effective than amitriptyline. A highly significant correlation was noted between improvement and MAO inhibition within the phenelzine group.", "We are performing a double-blind trial with inward psychiatric patients. The indication for our psychotropic or psychotherapeutic intervention is mainly severe depression (= major depressive disorders DSM III). For a 3-week trial course trazodone (400 mg daily), amitriptyline (150 mg/die) or placebo capsules were given at random. All patients received the same type of cognitive behaviour therapy. The test battery consists of CGI, BPRS, HAMD, HAMA and AMDP; adverse drug reactions are documented as \"free reports\" (= freier Nebenwirkungsbericht). The interim results (until March 1987) will be presented. Our investigation indicates that it is probable that the trazodone treatment we used is equivalent to corresponding amitriptyline treatment.", "This paper presents the results from a large multicenter study, performed at three clinical research units in the USA. Prior to a three to seven days of placebo washout period, patients were randomly assigned to zimelidine, a potent and selective 5-HT reuptake blocker, amitriptyline or placebo. The scheduled treatment period was four weeks. Dosage range was 75-300 mg/day for active medications. The rating instruments were the Hamilton Depression Scale and the Clinical Global Impression scale. The side effects were recorded by using a side effect inventory (TESS). Vital signs, laboratory work including clinical chemistry, ECG, and plasma levels of drugs, were performed. In the main efficacy evaluation there were 229 depressed outpatients included, all having completed at least two weeks of treatment after the washout period. The patients treated with zimelidine as well as those treated with amitriptyline showed a significant improvement relative to the placebo treated patients. For the safety evaluation 263 patients were included. Side effects, in particular anticholinergic effects but also drowsiness and cardiovascular effects, were much less pronounced in the zimelidine group as compared to the amitriptyline group. Only marginal differences regarding side effects were reported for zimelidine compared to those reported for placebo.", "The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized parallel clinical trials conducted serially, we examined the significance of NA uptake for antidepressant activity. The racemic compound oxaprotiline (hydroxymaprotiline) is a highly specific inhibitor of NA uptake, whereas its R-(-) enantiomer levoprotiline is totally devoid of this property. Oxaprotiline significantly resembled amitriptyline in its antidepressant potential. Conversely, levoprotiline significantly resembled placebo in antidepressant potential. Therefore, NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant.", "A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo.", "The neuropsychological test performance of 76 hospitalized, depressed patients meeting RDC for the presence of affective disorder was assessed as part of a protocol involving amitryptyline (n = 53) or placebo (n = 23). Tests included the Trail-making Test (TMT), the Benton Visual Retention Test, and the Shipley-Hartford Scale. Clinical ratings and data concerning the characteristics of EEG sleep were also obtained. Analysis of data collected after a drug-free period of 2 weeks and again at the end of the protocol yielded the following conclusions. Base-line performance was inferior to norms for these tests, but for the TMT, scores were not as poor as that expected for brain-damaged patients. Poor performance was often associated with older age, the presence of psychotic features, and prolonged sleep latencies. Baseline Hamilton Rating Scale (HRS) was predicted best by TMT part B. However, this association was not as strong as that between HRS and poor sleep efficiency. Treatment with drug or placebo had little differential effect upon test performance over the course of the protocol. It is suggested that further research should utilize tests which have specificity in localizing cerebral lesions, so that any focal deficits in brain function in depression might be identified.", "We performed a randomized, double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in outpatients with major depression, in particular patients with mixed anxiety/depressive symptomatology. Overall, amitriptyline was more effective than zimelidine and placebo after 4 weeks of treatment. However, when those patients with more severe depression were specifically examined, both antidepressants were equal in efficacy and superior to placebo. We also found no evidence for a greater likelihood of a zimelidine-induced peripheral neuropathy in this study. The present results suggest that zimelidine may be more effective in the treatment of severely depressed patients, rather than those with more mild mixed anxiety/depressive syndromes.", "A double-blind multicenter evaluation compared the antidepressant efficacy of bupropion (Wellbutrin) to both placebo and amitriptyline (Elavil, Endep) in adult patients who met DSM-III criteria for major depressive disorder. Steady-state plasma samples were obtained 11-12 hours and 4 hours after the last dose in 50 and 44 patients, respectively, who were treated for 6 weeks with bupropion. There was a curvilinear relationship between antidepressant efficacy and trough plasma bupropion concentrations, with maximum response observed at 5-100 ng/ml and virtually none below 25 ng/ml. The increase in plasma bupropion concentration from the trough level to the 4 hour postdose peak level was also positively related to antidepressant response.", "Speed of onset of antidepressant effect was studied in 20 depressed outpatients assigned double-blind to equipotent doses of amoxapine or amitriptyline. In counter-balanced order, each patient had 2 periods of 3 weeks on active agent interspersed with 2 similar periods of placebo control. On daily and weekly self-ratings, amoxapine was found to reduce symptoms significantly more rapidly than amitriptyline. Psychiatrist-ratings were consonant with self-reports.", "General practice depressives were treated for 6 weeks with amitriptyline or placebo in a controlled trial. Overall, drug was found strongly superior to placebo. Interactions were examined between drug effects and a number of variables, principally reflecting demographic characteristics, history of illness, severity of illness, and endogenous depression separately in symptoms and stress. Only in the area of severity were significant interactions found. Amitriptyline was superior to placebo in probable or definite major depression on the Research Diagnostic Criteria, but not in minor depression. It was also superior to placebo in subjects with initial scores on the Hamilton Depression Scale of 13-15, and 16 or more, but not with lower scores. Findings indicate that tricyclic antidepressants are of considerable benefit in relatively mild depressions, except in the mildest range.", "Adinazolam, a triazolobenzodiazepine, was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives. Forty-eight patients entered the study, and 35 completed 6 weeks of evaluation. Patients were well matched in each of the groups. Initially, the adinazolam group showed more improvement than the placebo group, but this trend did not persist beyond day 7. The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups, and final scores were significantly better for amitriptyline. Depressive symptoms in the amitriptyline dropout group appeared improved, whereas in the adinazolam and placebo dropout groups they were unchanged or worse. Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo. Thus, amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo.", "Changes in appetite and weight were examined in a group of 47 carefully diagnosed primary depressives who were treated in a random design with either placebo (N = 17) or amitryptyline (N = 30) over a 35-day protocol. While the amitriptyline treated group as a whole showed a greater gain in weight than did the placebo group (4.5 vs. 0.5 lb, p less than 0.05), no differential effects could be demonstrated between drug responders and nonresponders. Likewise, while a consistent relationship between the self-report of decreased appetite and final weight change was noted in the placebo group, no simple relationship between final weight change and self-reported changes in appetite were apparent in the drug-treated patients. There was, however, a relationship between the report of decreased appetite and clinical severity of depression in the drug nonresponder subgroup despite significant weight gain during the protocol. Thus, weight change during this study period did not appear to show a simple relationship to corresponding clinical change. The clinical lore that has supported the notion that increased appetite and weight gain in patients being treated with tricyclic antidepressants are \"good\" signs cannot be confirmed by our findings.", "Forty-five patients suffering from a major depression were administered zimeldine, amitriptyline or placebo (15 patients in each group) in a double-blind controlled study. In the zimeldine group, seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration, fever, myalgias and arthralgias. In all patients presenting this syndrome, laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts. Three patients presented a mild proteinuria and hematuria. Although an immunological mechanism cannot be ruled out, several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity. The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed.", "Changes in alpha-2 adrenoreceptor density and affinity during antidepressant treatment were studied using 3H-yohimbine binding to human platelet membranes. Baseline measurements were conducted in 21 patients diagnosed as having major depressive disorder with melancholia, and an equal number of age and sex matched normal controls. No differences were observed in receptor density or binding between pre-treatment subject groups and normal matched controls. Subjects participated for 6 weeks in a trial of placebo, adinazolam, or amitriptyline. Alpha-2 adrenoreceptor binding was not significantly changed from baseline following antidepressant treatment." ]
"Amitriptyline is an efficacious antidepressant drug. It is, however, also associated with a number of side effects. Degree of placebo response and severity of depression at baseline may moderate drug-placebo efficacy differences."
"CD007045"
[ "11843249", "15499601" ]
[ "Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.", "Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer." ]
[ "SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively target high levels of ionising radiation to tumors within the liver. This trial was designed to measure any increased patient benefit by adding a single administration of SIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day infusion of floxuridine and repeated at monthly intervals, vs. the same chemotherapy alone.\n A phase III randomised clinical trial entering 74 patients was undertaken on patients with bi-lobar non-resectable liver metastases from primary adenocarcinoma of the large bowel. Patient benefit criteria assessed in the trial were tumor response, time to disease progression in the liver, overall survival, quality of life, and treatment related toxicity. Tumor response was measured by serial changes in both cross-sectional tumor areas and total tumor volumes, provided any response lasted not less than three months as well as changes in serum carcino-embryonic antigen (CEA).\n The partial and complete response rate (PR + CR) was significantly greater for patients receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The median time to disease progression in the liver was significantly longer for patients receiving SIR-Spheres in comparison to patients receiving HAC alone when measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two, three and five-year survival for patients receiving SIR-Spheres was 72%, 39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox regression analysis suggests an improvement in survival for patients treated with SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in grade 3-4 treatment related toxicity and no loss of quality of life for patients receiving SIR-Spheres in comparison to patients receiving HAC alone.\n The combination of a single injection of SIR-Spheres plus HAC is substantially more effective in increasing tumor responses and progression free survival than the same regimen of HAC alone.", "Selective internal radiation therapy (SIRT) with SIR-Spheres(R) is a new technique for selectively targeting high doses of radiation to tumours within the liver. The primary objectives of this randomised trial were to compare the response rate, time to progressive disease (PD), and toxicity of a regimen of systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a single administration of SIR-Spheres in patients with advanced colorectal liver metastases. The trial was designed to presage a larger trial that would have survival as the primary outcome.\n Twenty-one patients with previously untreated advanced colorectal liver metastases, with or without extrahepatic metastases, were randomised into the study.\n Using RECIST criteria, the response rate for 11 patients receiving the combination treatment was significantly greater than for 10 patients receiving chemotherapy alone (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD was greater for patients receiving the combination treatment (18.6 months vs. 3.6 months, P < 0.0005). Median survival was significantly longer for patients receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One patient in the combination arm died from chemotherapy induced neutropenic sepsis after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity events in patients receiving the combination treatment. There was no difference in quality-of-life over a 3 month period between the two treatments when rated by patients (P = 0.96) or physicians (P = 0.98).\n This small phase 2 randomised trial demonstrated that the addition of a single administration of SIR-Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy significantly increased both treatment related response, time to PD, and survival with acceptable toxicity. The combination of SIR-Spheres plus systemic chemotherapy is now the subject of ongoing trials to further define patient benefit.\n (c) 2004 Wiley-Liss, Inc." ]
"There is a need for well designed, adequately powered phase III trials assessing the effect of SIRT when used with modern combination chemotherapy regimens. Further studies are also needed for patients with refractory disease with a particular focus on the impact on quality of life."
"CD007368"
[ "15158629", "20882421", "20375190" ]
[ "Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial.", "Zinc supplementation in severe acute lower respiratory tract infection in children: a triple-blind randomized placebo controlled trial.", "A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal." ]
[ "Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs--chest indrawing, hypoxia, and tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital.\n In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2-23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospital's standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics.\n The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis.\n Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable.", "To evaluate the efficacy of zinc supplementation on duration of illness in children with severe acute lower respiratory tract infection (ALRTI).\n This randomized triple-blind placebo-controlled trial was conducted in pediatric emergency of a teaching referral hospital. Children in the age group of 2-24 months presenting to pediatric emergency with severe ALRTI were included. Eligible children were randomly allocated to zinc (n=53) or control (n=53) groups. Zinc group received 20 mg of elemental zinc per day (5 ml syrup per day) as a single daily dose for 5 days. Control group received an equal amount of placebo which was appropriately modified to give the taste, smell, color and consistency similar to zinc mixture. Primary outcome was 'time to be asymptomatic', a composite outcome defined as resolution of all four of the following: danger signs, respiratory distress, tachypnea and hypoxia in room air.\n Age, gender, nutritional status, pretreatment zinc levels and other demographic and clinical variables were similar in the two groups. 'Time to be asymptomatic' was comparable in the two groups (h; median (IQR): 60 (24-78) vs. 54 (30-72), P=0.98]. At any time point a similar proportion of children were symptomatic in both the groups. Time to resolution of respiratory distress, tachypnea, dangers signs and hypoxia were also similar in two groups. Duration of hospital stay was shorter by 9 h in the zinc group but the difference was statistically insignificant.\n Zinc supplementation did not reduce recovery time and duration of hospital stay in children with ALRTI. Larger randomized controlled trials are needed to evaluate role of zinc in ALRTI.", "Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed.\n Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common.\n In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia.\n One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30).\n Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733." ]
"Evidence provided in this review is insufficient to recommend the use of zinc as an adjunct to standard antibiotic therapy for pneumonia in children aged two to 35 months."
"CD002973"
[ "10988090" ]
[ "Continuous tracheal gas insufflation in preterm infants with hyaline membrane disease. A prospective randomized trial." ]
[ "In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing airway pressure over the entire period of mechanical ventilation while maintaining oxygenation. A total of 34 preterm newborns, ventilated in conventional pressure-limited mode, were enrolled in two study arms, to receive or not receive CTGI. Transcutaneous Pa(CO(2)) (tcPa(CO(2))) was maintained at 40 to 46 mm Hg in both groups to ensure comparable alveolar ventilation. Respiratory data were collected several times during the first day and daily until Day 28. Both groups were similar at the time of inclusion. During the first 4 d of the study, the difference between peak pressure and positive end-expiratory pressure was significantly lower in the CTGI group by 18% to 35%, with the same tcPa(CO(2)) level and with no difference in the ratio of tcPa(O(2)) to fraction of inspired oxygen (245 +/- 29 versus 261 +/- 46 mm Hg [mean +/- SD] over the first 4 d). Extubation occurred sooner in the CTGI group (p < 0.05), and the duration of mechanical ventilation was shorter (median: 3.6 d; 25th to 75th quartiles: 1.5 to 12.0 d; versus median: 15.6 d; 25th to 75th quartiles: 7.9 to 22.2; p < 0.05) than in the non-CTGI group. CTGI allows the use of low-volume ventilation over a prolonged period and reduces the duration of mechanical ventilation." ]
"There is evidence from a single RCT that TGI may reduce the duration of mechanical ventilation in preterm infants - although the data from this small study do not give sufficient evidence to support the introduction of TGI into clinical practice. The technical requirements for performing TGI (as performed in the single included study) are great. There is no statistically significant reduction in the total duration of respiratory support or hospital stay. TGI cannot be recommended for general use at this time."
"CD004107"
[ "7570436", "11405516", "8541826", "8793447", "11371411", "9616530", "10955751", "9476870", "2148702", "11844120", "9154850", "8605463", "9404750", "8148679" ]
[ "Peak flow based asthma self-management: a randomised controlled study in general practice. British Thoracic Society Research Committee.", "Benefit from the inclusion of self-treatment guidelines to a self-management programme for adults with asthma.", "The effects of a cognitive behavioural intervention in asthmatic patients.", "A controlled assessment of an asthma self-management plan involving a budesonide dose regimen. OPTIONS Research Group.", "Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation.", "One-year economic evaluation of intensive vs conventional patient education and supervision for self-management of new asthmatic patients.", "Influence of peak expiratory flow monitoring on an asthma self-management education programme.", "A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.", "Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.", "A randomized trial of peak-flow and symptom-based action plans in adults with moderate-to-severe asthma.", "Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization.", "Randomised comparison of guided self management and traditional treatment of asthma over one year.", "The effect of a peak flow-based action plan in the prevention of exacerbations of asthma.", "Effectiveness of routine self monitoring of peak flow in patients with asthma. Grampian Asthma Study of Integrated Care (GRASSIC)." ]
[ "Peak flow based asthma self-management plans have been strongly advocated in consensus statements, but convincing evidence for the effectiveness of this approach has been largely lacking.\n A randomised controlled trial was conducted in 25 general practices comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period.\n Seventy two subjects (33 in the self-management group and 39 in the planned visit group) completed the study protocol, but diary card data for at least three months were available on a total of 84 (39 in the self-management group and 45 in the planned visit group). Teaching self-management took longer than the planned visit review. In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 (85%) and 27 (82%) cases, respectively. There were no between group differences during the study period in terms of lung function, symptoms, quality of life, and prescribing costs. Only within the self-management group were improvements noted in disturbance of daily activities and quality of life. Possible explanations for these negative results include small numbers of subjects, the mild nature of their asthma, and inappropriate self-management strategies for such patients.\n Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes. Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances.", "This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma. In this prospective randomized controlled trial, 245 patients with stable, moderate to severe asthma were included. They were randomized into a self-treatment group (group S) and a control group (group C). Both groups received self-management education. Additionally, group S received self-treatment guidelines based on peak expiratory flow (PEF) and symptoms. Outcome parameters included: asthma symptoms, quality of life, pulmonary function, and exacerbation rate. The 2-yr study was completed by 174 patients. Both groups showed an improvement in the quality of life of 7%. PEF variability decreased by 32% and 29%, and the number of outpatient visits by 25% and 18% in groups S and C, respectively. No significant differences in these parameters were found between the two groups. After 1 yr, patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma. The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups. Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma. However, patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group.", "There is evidence that educational programmes may improve patient's compliance with asthma treatment and control symptoms. Whilst medical parameters have been thoroughly studied, few data are available concerning psychological intervention. The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group (ARG) and in a Control Group (CG). Forty consecutive asthmatics were randomly enrolled, all of whom were diagnosed, treated and followed-up according to the International Guidelines. Both groups underwent a psychological assessment at baseline and after one year. A battery of questionnaires was used to obtain data relating to baseline characteristics (anxiety, depression, psychophysiological disorders), emotional reactions to asthma attacks (panic-fear, etc,) and cognitive variables (external control, psychological stigma, internal beliefs, external chance, etc.) involved in the perceived illness. In addition, the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention. In both groups, a reduction of anxiety and depression scores was observed, as well as a significant improvement of the medical parameters evaluated. Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Questionnaire and on the External Control Subscale after 1 year. The Control Group reported higher score on the External Chance Scale. The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma. Larger scale studies on this topic are suggested.", "Our aim was to assess the efficacy of budesonide (Pulmicort Turbohaler Astra) used as part of a self-management plan in a group of patients with chronic asthma. One hundred and twenty five patients with nocturnal asthma symptoms, despite the use of inhaled prophylactic and beta 2-agonist therapy, were randomized to inhaled budesonide 200, 400 or 800 micrograms b.i.d. either with dose adjustments made by the physician, i.e. doctor-managed (DM; n = 64), or as part of a self-management plan (SM; n = 61). The SM group were allowed to adjust their dose according to written guidelines based on morning peak flow. At the end of the 6 month treatment period, there were no significant differences detected between the DM and the SM groups either from the clinic or diary card data. Both groups demonstrated a significant reduction in the number of sleep-disturbed nights, by 75% in the DM group and 77% in the SM group, at the end of the study. In conclusion, for patients with mild-to-moderate asthma, either a doctor-adjusted dose regimen or a peak flow based self-management plan involving budesonide is equally efficacious. For some patients, a simple regimen, adjusted by the physician at clinic visits, may be easier to follow.", "Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.", "The purpose was to compare the short-term cost-effectiveness of intensive vs conventional education and supervision for the self-management of mild asthmatic patients. Consecutive newly diagnosed asthmatic patients (n = 162) were randomized into an intervention group (IG) and a control group (CG) with 1 yr of treatment and follow-up. Intensive education was given to 77 patients at visits every third month in the outpatient clinic. Eighty CG patients received conventional education and advice at the baseline visit only. All patients received similar inhaled anti-inflammatory treatment. At baseline and at 12 months standard clinical lung functions and health-related quality of life (HRQOL) were measured, the latter by the disease-specific St George's Respiratory Questionnaire and the generic 15D. Furthermore, the use of extra health care services, medication and sickness days were recorded. The IG experienced a significant improvement in all clinical and HRQOL outcome variables. The same applied to the CG except spirometric values. The groups differed significantly only in terms of FEV1 (P < 0.05) in favour of the IG. There was a significant difference between the groups in extra costs. The mean cost was FIM 2351 per patient (294 Pounds sterling) in the CG and FIM 2757 per patient (345 Pounds) in the IG, of which the intervention cost was FIM 1978 per patient (247 Pounds). In 1 yr follow-up the intensive education programme did not prove to be cost effective but was dominated by the conventional one regardless of what effectiveness measure was used. Also, a purely monetary cost-benefit calculation showed that the intervention resulted in a negative net benefit (loss) of FIM 406 per patient (51 Pounds). A longer follow-up may be needed before definitive conclusions about the cost-effectiveness of this kind of intervention can be drawn.", "We assessed whether peak expiratory flow monitoring added to a self-management education programme reduced morbidity and improved pulmonary function and adherence to treatment in 100 asthma patients (aged 17-65 years) with adequate treatment and regular 1-year follow-up. Patients randomized to the experimental group used peak expiratory flow readings as the basis for their therapeutic plan coupled with educational intervention, whereas patients in the control group received the same educational intervention and used symptoms only to guide self-management. Morbidity parameters, functional status and adherence to medical regimens improved in both groups, although the percentage of patients with satisfactory adherence was significantly better in the group with peak expiratory flow monitoring (83%) than in controls (52%) (P = 0.05). The multivariate analysis showed that severity of asthma (odds ratio 9.28, 95% confidence interval 1.87-45.96, P = 0.006 for moderate asthma) and type of self-management education programme (odds ratio: 6.19; 95% confidence interval: 2.04-18.81; P = 0.001 for the use of peak expiratory flow readings) were the only independent predictors of adherence to treatment. However, a statistically significant association between adherence and use of peak expiratory flow monitoring was only found in patients with moderate asthma (P = 0.0009). We conclude that peak expiratory flow monitorization in optimal conditions (adequate medical regimen, individualized self-management education and regular follow-up) showed a beneficial effect on adherence to prescribed regimens only in patients with moderate asthma.", "Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.", "To compare a peak flow self management plan for asthma with a symptoms only plan.\n Randomisation to one of the self management plans and follow up for a year.\n Four partner, rural training practice in Norfolk.\n 115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic.\n The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol.\n Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group.\n The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.", "Peak flow meters (PFM) continue to be recommended as an important part of asthma self-management plans. It remains unclear if there is an advantage in using PFM in people with moderate-to severe asthma who are not poor perceivers of bronchoconstriction.\n Prospective, randomized controlled trial of 134 adults with moderate-to-severe asthma who did not have evidence of poor perception of bronchoconstriction on histamine challenge testing, who were recruited from inpatients and outpatients of a university teaching hospital. Comparison was made over 12 months of the effectiveness of written action plans using either peak flow monitoring or symptoms to guide management. Subjects were contacted at monthly intervals by telephone for reinforcement and evaluation of use of the action plans, and to provide ongoing education. Spirometry and PD20 histamine were measured at 3-monthly intervals. Measures of health care utilization and morbidity (asthma exacerbations; hospitalizations; emergency department (ED) visits; days absent from work or school due to asthma; medication use and a self-rating of asthma severity) were made monthly. A psychosocial questionnaire (attitudes and beliefs, state-trait anxiety, denial) was given at entry and at 12-months or at withdrawal from the study.\n There were significant improvements for both groups for hospitalizations, ED visits, days off from school or work, and PD20 histamine, but no between-group differences. Appropriate use of action plans was 85% in the symptoms group and 86% in the PFM group. For all subjects, those who subsequently had an ED visit had significantly higher levels of denial (P=0.04) and lower scores for self-confidence (P=0.04), compared to those who did not have an ED visit.\n Use of written action plans, combined with regular contact to reinforce self-management, improved airway reactivity and reduced health care utilization. However, use of PFM was not superior to symptom-based plans.", "The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity, knowledge, and compliance with inhaled corticosteroid treatment using a prospective, randomized, controlled, one-year-before/one-year-after protocol. After rigorous optimization of asthma therapy under the care of respirologists, patients were assigned to one of three groups: Group C (control group: no formal education), Group P (education and action plan based on peak-flow monitoring), and Group S (education with action plan based on monitoring of asthma symptoms). A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study. Asthma morbidity decreased significantly in all groups (p = 0.001). Mean values one-year-before/one-year-after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7, and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2, 8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical significance (p > 0.05). Asthma knowledge increased in both educated groups compared with the control group (p < 0.001) as did short-term compliance with inhaled corticosteroids. These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity. In such clinical settings, structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma, although it could not add extra benefit with regard to morbidity. Nevertheless, this study does not refute the potential benefit of educational interventions aimed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors.", "To compare the efficacy of self management of asthma with traditional treatment.\n 12 month prospective randomised trial.\n Outpatient clinics in Finland.\n 115 patients with mild to moderately severe asthma.\n Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements.\n Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life.\n The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare.\n Self management reduces incidents caused by asthma and improves quality of life.", "To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma.\n A randomized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan, a symptom-based plan, or a peak flow-based action plan.\n A university hospital asthma clinic.\n One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma.\n All subjects received evaluation and education for asthma before being randomly allocated to receive no action plan, a symptom-based action plan, or a peak flowmeter and a peak flow-based action plan.\n Subjects were assessed by questionnaire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma.\n At 6 months after enrollment, although all three intervention groups experienced improvement in their asthma control, there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group (p=0.006). No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups.\n We conclude that a peak flow-based action plan is effective, at least in the short term, in protecting patients with asthma against severe exacerbations of their disease.", "To evaluate the effectiveness of routine self monitoring of peak flow for asthma outpatients.\n Pragmatic randomised trial.\n Hospital outpatient clinics and general practices in north east Scotland.\n Use of bronchodilators and inhaled and oral steroids; number of general practice consultations and hospital admissions for asthma; sleep disturbance and other restrictions on normal activity; psychological aspects of health including perceived control of asthma.\n After one year there were no significant differences between patients randomised between self monitoring of peak flow and conventional monitoring. However, those given a peak flow meter recorded an increase in general practice consultations that was nearly significant. Among patients whose asthma was judged on entry to be more severe, those allocated to self monitoring used more than twice as many oral steroids (2.2; 95% confidence interval 1.1 to 4.6). Patients who already possessed a peak flow meter at the start of the study recorded higher morbidity over the course of the year than those eligible for randomisation.\n Prescribing peak flow meters and giving self management guidelines to all asthma patients is unlikely to improve mortality or morbidity. Patients whose asthma is severe may benefit from such an intervention." ]
"Optimal self-management allowing for optimisation of asthma control by adjustment of medications may be conducted by either self-adjustment with the aid of a written action plan or by regular medical review. Individualised written action plans based on PEF are equivalent to action plans based on symptoms. Reducing the intensity of self-management education or level of clinical review may reduce its effectiveness."
"CD002879"
[ "1361594", "9655732", "3541946", "2844548", "359091", "7000127", "9228354", "3282826", "3296296", "6998599", "2236929", "8323338", "2856542" ]
[ "Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma.", "Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group.", "Twice daily administration of beclomethasone dipropionate dry-powder in the management of chronic asthma.", "Effects of inhaled beclomethasone dipropionate on beta 2-receptor function in the airways and adrenal responsiveness in bronchial asthma.", "Beclomethasone dipropionate dry-powder inhalation compared with conventional aerosol in chronic asthma.", "Beclomethasone dipropionate in asthma: a comparison of two methods of administration.", "A comparison of double-strength beclomethasone dipropionate (84 microg) MDI with beclomethasone dipropionate (42 microg) MDI in the treatment of asthma.", "Six-month double-blind, controlled trial of high dose, concentrated beclomethasone dipropionate in the treatment of severe chronic asthma.", "Twice daily beclomethasone dipropionate administered with a concentrated aerosol inhaler: efficacy and patient compliance.", "Beclomethasone dipropionate aerosol compared with dry powder in the treatment of asthma.", "Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma.", "Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate.", "Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects." ]
[ "It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device.", "Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 microg twice daily (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 microg twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication.", "In a double-blind cross-over study beclomethasone dipropionate inhaled as a dry-powder in a dose of 400 micrograms twice daily was compared with a conventional aerosol in a dose of 100 micrograms four times daily in 16 outpatients with chronic asthma. Each of the 2 treatments lasted for 4 weeks. There was no significant difference with respect to daily peak expiratory flow rates, symptom scores, bronchodilator usages and other lung function measurements between the 2 treatments. Tetracosactrin tests were within normal limits and no clinical oral candidiasis was observed throughout the study. In conclusion, beclomethasone dipropionate dry-power given twice daily was effective for the control of asthma and could be recommended for patients with poor drug compliance.", "Sixteen patients suffering from bronchial asthma, with or without chronic bronchitis, sufficiently severe to be treated with inhaled corticosteroids, were studied in a single-blind trial (blind observer) of beclomethasone dipropionate (BDP) given in three randomized dosage regimens: 500, 1000 and 2000 micrograms per day, each for 4 weeks. The beta 2-adrenergic agonist response curve showed a dose-dependent increase in FEV1 which was not affected by different doses of BDP. A small but significant reduction in basal cortisol levels was observed after BDP 500 micrograms/day. There was no significant difference between the various doses of BDP in reducing cortisol level and stimulation with tetracosactide remained unchanged. The study showed a gradual, dose-dependent improvement in lung function, statistically significant for morning peak expiratory flow rate at BDP 2000 micrograms/day. Dyspnoea score and beta 2-agonist use decreased, reflecting the anti-asthmatic effects. An increase in total leukocyte count was observed, together with a decrease in the eosinophil count. Oral candidiasis was seen in 2 out of 16 patients. It is concluded that the clinical anti-asthmatic effects of corticosteroid treatment by inhalation are not due to modulation of beta 2-receptor function in the airways.", "In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.", "Beclomethasone dipropionate inhaled as a dry powder in doses of 200 microgram four times a day was compared with the usual dose of 100 microgram four times a day from a pressurized aerosol in 65 patients with asthma who used pressurized aerosols correctly. Each treatment was given for an eight-week period. The dry powder did not show any clinically significant advantage over the aerosol in terms of ventilatory function as measured by FEV1 and the daily peak flow measurements during both treatments did not differ. The incidence of oral candidiasis was low and no other side-effects were encountered. It was concluded that beclomethasone dipropionate in dry powder form was as effective as aerosol in the treatment of asthma.", "To compare the efficacy and safety of a double-strength formulation of beclomethasone dipropionate (BDP 84) metered-dose inhaler (MDI) with that of beclomethasone dipropionate (BDP 42) MDI in the treatment of chronic asthma.\n A 28-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter study.\n Outpatient.\n A total of 423 patients aged 12 to 65 years (mean range, 34 to 36 years) with moderate asthma (FEV1, 50 to 80% of predicted) who required long-term inhaled corticosteroids were enrolled.\n Patients were randomized to receive BDP 84, two oral inhalations bid (336 microg/d), BDP 42, four oral inhalations bid (336 microg/d), or placebo. A fourth treatment arm administering BDP 84, eight oral inhalations bid (HD BDP 84; 1,344 microg/d) was also included to determine whether a dose-response relationship could be demonstrated.\n Spirometry, clinical observations.\n The three active treatments were significantly more effective (p < or = 0.01) than placebo at all time points in improving FEV1, the primary efficacy parameter; BDP 42 and BDP 84 were comparable to each other at every time point. Secondary pulmonary function tests (FVC, forced expiratory flow at 25 to 75% of FVC, and peak expiratory flow rate) showed similar results. All three active treatments were well tolerated. A dose response between 336 microg/d and 1,344 microg/d was demonstrated.\n In this well-controlled 28-day study, BDP 42 and BDP 84 were shown to be comparable in efficacy and safety on a microgram-for-microgram basis.", "A six-month double-blind controlled trial compared a 2,000 microgram per day dose of beclomethasone dipropionate aerosol (BDP), with current upper level doses of 800 micrograms per day of the standard BDP, in asthmatics requiring oral corticosteroids in addition to BDP and bronchodilators. Both groups showed a significant reduction in their oral steroid requirements during the study, with a 34 percent reduction in the lower dose group and a 57 percent reduction in the high dose BDP group while maintaining good symptomatic control of asthma; there was an associated improvement in baseline serum cortisol levels. Over the same period, the pulmonary function of the lower dose group showed significant worsening relative to that of the group receiving the high dose BDP which improved. There was no increase in dysphonia or oropharyngeal candidiasis among those using the concentrated BDP. We conclude that high dose concentrated BDP appears to be a safe medication in long-term steroid-dependent asthma, and is effective in reducing dependence on the use of oral corticosteroid with associated improvement both in pulmonary and adrenal function.", "The efficacy of twice daily inhaled beclomethasone dipropionate administered by a concentrated aerosol inhaler (one puff twice daily-500 micrograms/day) has been compared with that of treatment four times daily with a standard dose inhaler (two puffs four times daily-400 micrograms/day) in 21 patients with stable asthma. Double placebo inhalers were used in a randomised crossover fashion during two four week treatment periods. Mean peak expiratory flow (PEF), mean symptom scores, and number of extra salbutamol inhalations required were not significantly different between the two treatment periods. Local side effects were more common during treatment with the four times daily active preparation; overt oropharyngeal candidiasis, however, was not found in either group during the study. On completion of the crossover study patients were transferred to the twice daily regimen. At the three month follow up all patients had remained stable and the outpatient PEF was significantly higher (mean 382 (SD 26)l min-1) than at entry into the trial (mean 345 (24)l min-1) (p less than 0.05). Twice daily beclomethasone administered by a concentrated aerosol inhaler appears to be as effective as the standard four times daily regimen in controlling stable asthma.", "In a double-blind trial, beclomethasone dipropionate inhaled as a dry powder in doses of 200 micrograms three times a day was compared with the conventional aerosol of 100 micrograms three times a day, each for a period of 4 weeks. Neither the dry powder nor the aerosol showed any significant advantage over each other in terms of ventilatory function. Plasma cortisol levels were unaltered with the two medications in spite of the doubled dose of the corticosteroid powder. Choice of one or the other method of administration of medication depended on patient preference and the ease with which he could familiarize himself with either technique.", "The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.", "Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate, 400 micrograms, and 800 micrograms beclomethasone dipropionate from a dry powder inhaler. The design was a randomised, double blind, crossover trial. After a run in period of four days (period 1) the children were allocated to a sequence of active treatments in periods 2, 4, and 6. In periods 3 and 5 (wash out) placebo was given. All periods except the run in were two weeks long. The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week. Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34, 0.09, and 0.06 mm/week respectively. Compared with fluticasone propionate, treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity.", "To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 micrograms bid), high dose beclomethasone aerosol (1000 micrograms bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (+/- SE) value of FEV1 4 h after exposure to TDI was 2.6 +/- 0.17 L, which went to 3.3 +/- 0.12 after low dose beclomethasone, and to 3.5 +/- 0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P less than 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63).(ABSTRACT TRUNCATED AT 250 WORDS)" ]
"BDP appears to demonstrate a shallow dose response effect in long-term asthma for a small number of efficacy outcomes over range of daily doses from 400 mcg/d to 1600 mcg/d, although the clinical significance of the improvements afforded by higher doses is questionable."
"CD002086"
[ "6216858", "131678", "3157706", "138560", "1981436", "12695127", "9649660", "16312705", "150346", "14988688", "17436825", "2938993", "11867968", "11701404", "16702498", "21269305", "2965628", "15588555", "17436826", "2530191", "11586012" ]
[ "Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris.", "Minocycline in acne vulgaris: a double-blind study.", "An accurate photographic method for grading acne: initial use in a double-blind clinical comparison of minocycline and tetracycline.", "Minocycline therapy in acne vulgaris.", "A double-blind comparison of topical clindamycin and oral minocycline in the treatment of acne vulgaris.", "Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline.", "A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris.", "Josamycin versus minocycline in the treatment of papulopustular acne.", "Minocycline versus doxycycline in the treatment of acne vulgaris. A double-blind study.", "A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris.", "Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris.", "Isotretinoin versus minocycline in cystic acne: a study of lipid metabolism.", "Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy.", "Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne.", "Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study.", "Efficacy of oral antibiotics on acne vulgaris and their effects on quality of life: a multicenter randomized controlled trial using minocycline, roxithromycin and faropenem.", "Efficacy of low-dose cyproterone acetate compared with minocycline in the treatment of acne vulgaris.", "Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.", "Safety and efficacy of a new extended-release formulation of minocycline.", "[Treatment of acne vulgaris. A comparison of doxycycline versus minocycline].", "Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris." ]
[ "A double-blind evaluation of the efficacy and safety of minocycline hydrochloride and tetracycline hydrochloride was conducted and completed using 49 patients with Pillsbury grade 2 or grade 3 acne. For six months, half of the patients received minocycline and half received tetracycline. Although the differences between treatment groups were not statistically significant at any evaluation, more patients treated with minocycline reached and maintained a noninflammatory acne status in less time than did patients treated with tetracycline. After six weeks, twice as many patients in the group treated with minocycline had reached noninflammatory status. Side effects reported by 7 patients were equally distributed between treatment groups. No notable abnormalities were observed in the results of blood chemistry studies, hematologic tests, quantitative serum immunoglobulin determinations, or thyroid function tests in 20 of the patients examined.", "nan", "This investigation utilized an accurate photographic method and grading scale for evaluating acne in sixty-two patients. During a randomized double-blind clinical study in which half of the patients received minocycline and half, tetracycline, photographs of facial or body acne were taken at baseline and every 2 weeks over a 12-week period of therapy. In addition to on-site blinded gradings by both the investigator and the patients, separate assessments were made by two independent dermatologists utilizing the scale and the transparencies taken during the study. A reasonable agreement was found between the investigator, the patients, and the independent dermatologists, indicating the usefulness of this method. The investigator's rating of acne severity disclosed a significantly (p less than or equal to 0.05) more rapid clinical response at weeks 2 and 8 in the patients who received minocycline than in those who received tetracycline. Also, the assessment of one of the independent dermatologists showed a significantly (p = 0.024) better response to minocycline than to tetracycline at week 8 of therapy. The incidence of adverse clinical experiences was lower in the minocycline-treated group (10%) than in the tetracycline-treated group (22%).", "A double-blind, random distribution study showed that a lower than recommended dose of minocycline--50 mg twice daily--was as effective as a dose of 250 mg twice daily of tetracycline for treatment of acne vulgaris in comparable patient groups, and that minocycline produced no vestibular side effects at the lower dosage. Like tetracycline, minocycline did not produce the phototoxicity associated with demeclocycline or the life-threatening colitis associated with clindamycin. Patients in this study did not develop a resistance either to minocycline or to tetracycline. Studies of the use of minocycline in patients who have developed tetracycline resistance and long-range studies of patients on the new lower dose of minocycline are now underway.", "Sixty-six patients with moderate to severe facial acne vulgaris were entered in a 12-week double-blind study to compare the efficacy of topical clindamycin phosphate 1% twice daily and oral minocycline 50 mg twice daily. Both treatments gave significant overall improvements from baseline observations in acne grade and inflamed lesion counts, but not in noninflamed lesion counts. There were no significant differences between the two treatment groups in respect of acne grade, inflamed or non-inflamed lesion counts. Both treatment regimes were well tolerated. This study has shown that topical clindamycin twice daily is an effective alternative to oral minocycline 50 mg twice daily in the treatment of moderate to severe facial acne vulgaris.", "A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective.", "A multicentre, randomised, double-blind and double-dummy study was conducted to compare the efficacy and safety of lymecycline (n = 71) with that of minocycline (n = 73) in 144 patients with moderately severe acne vulgaris. Patients with an acne score of 1-5 on the Leeds scale received oral lymecycline, 300 mg/day for 2 weeks, then 150 mg/day for 10 weeks or oral minocycline, 100 mg/day for 2 weeks then 100 mg every other day for 10 weeks. Inflammatory, non-inflammatory and total lesion counts were determined at baseline (week 0) and after 4, 8 and 12 weeks' treatment, and global efficacy and safety assessments were made by the patient and investigator at the end of the study. Both treatments were equally effective at reducing differential lesion counts and improving acne condition and severity, with no significant differences between treatments. Inflammatory lesions were reduced by 50.6% and 52.2% with lymecycline and minocycline, respectively, and non-inflammatory lesions by 40.6% and 32.2%. Acne severity was reduced by 42.4% with lymecycline and by 47.9% with minocycline. A total of 4.3% of lymecycline recipients and 4.1% of minocycline recipients experienced treatment-related adverse events, the majority of which were mild in nature. Lymecycline was as effective as minocycline for the treatment of moderately severe acne vulgaris. Both treatments were well tolerated, although there were slightly fewer adverse gastrointestinal and dermatological effects with lymecycline.", "nan", "nan", "Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.", "A multicenter, 12-week, randomized, double-blinded, placebo-controlled, dose-ranging study was conducted in 233 subjects with moderate to severe facial acne vulgaris to determine the lowest effective once-daily oral dose of a new extended-release (ER) minocycline hydrochloride formulation with the safest adverse effect profile. Subjects randomly were assigned to treatment with daily dosages of ER-minocycline 1-, 2-, or 3-mg/kg tablets, or daily placebo tablets, for 84 days. At the end of the 12 weeks, the number of inflammatory lesions decreased approximately 50% from baseline levels in the dose groups. No dose-dependent effect was observed, with the percentage decrease in the number of inflammatory lesions in the 1-mg/kg treatment group being equal to or greater than higher doses. The pairwise difference between the ER-minocycline 1 mg/kg and placebo groups in the percentage decrease in inflammatory lesions was statistically significant (P = .015). Acute vestibular adverse events (AVAEs) appeared to be dose proportional, with the incidence being similar in the lowest (1 mg/kg) dosing group (24%) and in the placebo group (26%). Higher-dose regimens were associated with a higher incidence of central nervous system side effects and AVAEs. A 1-mg/kg daily dosage of the new ER-minocycline formulation is the lowest effective dose with the safest side effect profile, with higher-dose regimens offering no substantial therapeutic advantages.", "We have recently reported that patients with severe nodular cystic acne have much lower levels of HDL-cholesterol, apolipoprotein A and hepatic lipoprotein lipase than healthy controls or subjects with acne vulgaris. Since isotretinoin is very effective in the treatment of the nodular cystic acne but has been shown to increase blood lipid levels, we decided to compare its clinical effectiveness and its effects on lipid metabolism with those of minocycline in patients with nodular cystic acne. After 20 weeks, the number and mean diameter of the cysts were definitely decreased in both groups, but the improvement was more striking in the isotretinoin-treated group. At the end of the treatment, the HDL-C and hepatic lipoprotein lipase levels in this group were increased toward normal, but not in the minocycline-treated group. Our study showed a significant remission in the acne of patients treated with isotretinoin but not in that of the minocycline-treated patients. Furthermore isotretinoin can also correct the altered lipid metabolism in these patients.", "Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare.\n To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages.\n Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings.\n Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria.\n In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.\n Copyright 2002 S. Karger AG, Basel", "The primary aim of the study was to establish the clinical efficacy and safety of a combined treatment consisting of topical 20% azelaic acid (AA) cream and the oral antibiotic minocycline in the therapy of severe inflammatory acne (nodular papulopustular acne and acne conglobata) in a comparison with oral isotretinoin therapy. The secondary aim was to establish the value of AA cream as maintenance therapy in the prevention of recurrent acne.\n This open-label but randomised study involved 85 patients with nodular papulopustular acne or acne conglobata (Leeds grading scale > 4) who were treated for 6 months. In an immediately subsequent 3-month second phase, eligible patients from the initial combination group used the AA cream as maintenance therapy, while the eligible patients from the isotretinoin group served as untreated control.\n A 6-month course of treatment with topical 20% AA cream plus oral minocycline in 50 patients proved to be effective in nodular forms of acne (median reduction of facial comedones: 70%; of papules and pustules: 88%; of deep inflammatory acne lesions: 100%). Overall, the combined treatment was not quite as effective as treatment with oral isotretinoin (35 patients; reduction of comedones: 83%; of papules and pustules: 97%; of deep inflammatory acne lesions: 100%). In the 3-month maintenance therapy phase, about half of the patients who received AA monotherapy maintained the very good facial result achieved by the end of phase I. A similar rate was found in the patients of the isotretinoin group, who received no further active acne treatment. In the other 50% of patients, differences existed between the groups as regards the degree of deterioration: Marked deterioration occurred more frequently under AA treatment, while only slight deterioration was more frequent in the isotretinoin group. The combination was tolerated much better than isotretinoin. The incidence of local side effects observed under the combination of AA and minocycline (36.5%, mainly transient burning and itching of mild or moderate intensity) was considerably lower than that seen with isotretinoin (65.7%). The rate of local side effects of marked intensity observed under the combination, i.e. 6%, was well within the range of 5-10% previously reported for AA. The incidence of systemic side effects was lower (8%, mainly gastrointestinal symptoms) under the combined therapy than under isotretinoin (14.3%).\n The combination of topical 20% AA cream and oral minocycline is an highly effective treatment in severe forms of acne. It is better tolerated and associated with fewer risks than oral isotretinoin - in particular, there is no risk of teratogenicity. The combination can be regarded as a valuable alternative in patients for whom isotretinoin is not indicated, who do not wish to use or can not tolerate isotretinoin therapy and particularly in female acne patients of child-bearing potential. Topical 20% AA cream can be used successfully as maintenance therapy to prolong the recurrence-free interval.", "To evaluate the efficacy of 3 maintenance regimens (topical tazarotene, oral minocycline hydrochloride, or both) in sustaining improvement in acne.\n Multicenter, open-label treatment phase followed by double-blind, randomized, parallel-group maintenance phase.\n Ambulatory patients in research or referral centers.\n Volunteer sample of 189 patients with moderately severe to severe acne vulgaris (110 entered maintenance phase, 90 completed, and 2 discontinued because of adverse events).\n All patients were treated with 0.1% tazarotene gel (each evening) and a 100-mg capsule (twice daily) of minocycline hydrochloride for up to 12 weeks. Patients with 75% or greater global improvement at week 12 were randomly assigned to 12 weeks of maintenance therapy with tazarotene gel plus placebo capsules, vehicle gel plus minocycline capsules, or tazarotene gel plus minocycline capsules.\n Overall disease severity, global improvement, and lesion counts.\n All regimens were effective in sustaining improvements in acne. After 12 weeks of maintenance therapy, the mean reductions from baseline in noninflammatory and inflammatory lesion count, respectively, were 60% and 54% with tazarotene, 52% and 66% with minocycline, and 64% and 66% with tazarotene plus minocycline. At week 24, more than 80% of patients in each group had maintained a 50% or greater global improvement from baseline, and more than 50% had maintained a 75% or greater global improvement.\n A high percentage of patients with moderately severe to severe acne can maintain improvement in their condition with topical retinoid monotherapy. Maintenance with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance vs tazarotene alone. Topical retinoid monotherapy should be considered for maintenance to help minimize antibiotic exposure.", "There are few clinical studies which compare the efficacy and patient satisfaction for oral antibiotics to treat inflammatory acne. To clarify the difference between oral antibiotics, acne patients with moderate to severe inflammatory eruptions were randomized into three groups, and each patient was given minocycline (MINO), roxithromycin (RXM) or faropenem (FRPM) for 4 weeks, followed by 4 weeks of observation without any oral antibiotics. We estimated the reduction rate of inflammatory lesion counts, the scale of Skindex-16 which represents patient quality of life (QOL), and minimum inhibitory concentrations required to inhibit the growth of 90% of Propionibacterium acnes isolated from acne patients (MIC(90) ). In all three groups, inflammatory lesion counts, and emotional and total score of Skindex-16 were significantly improved (P<0.05) after 4 weeks treatment, and these effects were maintained for the following 4 weeks. Dizziness/nausea in two patients (4.1%) of the MINO group and diarrhea in three patients (5.9%) of the FRPM group were observed. There was no significant difference of percentage reduction in inflammatory lesion counts and incident rates of side-effects between these three oral antibiotics. MIC(90) of MINO was 0.25 μg/mL before and after treatment, but MIC(90) of RXM had increased from 0.25 μg/mL to more than 32 μg/mL after treatment. MIC(90) of FRPM was 0.06 μg/mL or less for all strains before and after treatment. Our randomized controlled clinical trial suggested that MINO, RXM and FRPM were efficient to improve inflammatory acne and patient QOL, and there was no significant difference between them.\n © 2010 Japanese Dermatological Association.", "nan", "To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains.\n This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks.\n Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England.\n Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face.\n Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group).\n The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots).\n The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study.\n The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).", "The complete safety and efficacy of a new extended-release (ER) minocycline hydrochloride formulation were assessed in an analysis of a phase 2 dose-finding study and 2 phase 3 safety and efficacy studies. The studies were similar in design, subject populations, and shared common dose groups of subjects given ER minocycline 1 mg/kg daily or placebo over 12 weeks. The similar designs were prospective, multicenter, randomized, double-blinded, and placebo-controlled. A total of 1038 subjects with moderate to severe acne were available for the pooled analysis. Independently, each study showed that treatment with ER-minocycline significantly reduced (P < .001) the number of inflammatory lesions and significantly improved (P < .001) their Evaluator's Global Severity Assessment (EGSA) scores (phase 3 studies). Analysis of the pooled population confirmed the results of the individual studies. The percentage of subjects reporting acute vestibular adverse events (AVAEs) was comparable between those receiving the ER-minocycline 1-mg/kg dose and placebo (approximately 10% of subjects in each group) for both the individual studies and the pooled population. It was concluded that a novel ER-minocycline formulation that delivers consistent levels of drug at a 1-mg/kg dose reduces dose-dependent AVAEs while reducing inflammatory lesions and improving the overall appearance of patients with acne vulgaris.", "In the course of a randomized, comparative, clinical study, 50 patients with acne vulgaris received systemic treatment with a single daily dose of 50 mg doxycycline or two daily doses of 50 mg minocycline. At the completion of the 12-week treatment, cure or improvement of acne was found in 78% of the patients in the doxycycline group compared to 82% in the minocycline group. The rate of unsatisfactory therapeutic results was 22% in the doxycycline group and 18% in the group of patients treated with minocycline. The results showed no significant difference between the clinical efficacy of treating acne vulgaris with doxycycline at a daily dose of 50 mg and 100 mg of minocycline daily, a fact which has already been demonstrated by earlier studies.", "In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne.\n To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris.\n Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules).\n This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline).\n Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.\n Copyright 2001 S. Karger AG, Basel" ]
"Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines."
"CD007598"
[ "11984383", "19731848", "10434220", "14770380", "17304779", "12776641", "9378876" ]
[ "Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting.", "Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified as at high risk for developing PONV.", "An alternative method to alleviate postoperative nausea and vomiting in children.", "Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea.", "A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home.", "Comparison of inhaled isopropyl alcohol and intravenous ondansetron for treatment of postoperative nausea.", "Peppermint oil: a treatment for postoperative nausea." ]
[ "The mechanisms for postoperative nausea and vomiting are numerous and pathways not well elucidated. Although many medications have been developed to help prevent postoperative nausea and vomiting, the search for better approaches to recovery treatment continues.\n The purpose of this study was to evaluate the effectiveness of isopropyl alcohol (IPA) inhalation for treatment of postoperative nausea and vomiting for patients who have general anesthesia for a surgical procedure.\n Participants were recruited from an urban hospital on the East Coast of the United States. Participants were assigned to an experimental or control group and IPA inhalation was compared to the standard anti-emetic treatment for rescue treatment in the immediate postoperative period. Postoperative nausea and vomiting was rated using a descriptive ordinal scale.\n The results of this study show IPA to be effective and that there was no significant difference between the standard treatment protocol and treatment with IPA. Treatment with IPA was significantly more cost effective than standard drug treatment.\n Further research is recommended to evaluate the length of effectiveness, standard dose needed, most effective mode of inhalation, and factors blocking IPA effectiveness.", "Frequently, patients identified as high risk for postoperative nausea and vomiting (PONV) are treated prophylactically with intravenous (IV) ondansetron and postoperatively with IV promethazine. The purpose of this study was to determine if using an aromatic therapy of 70% isopropyl alcohol (IPA) would be more effective than promethazine in resolution of breakthrough PONV symptoms in groups of high-risk patients administered prophylactic ondansetron. All subjects enrolled were identified as high risk for PONV, administered general anesthesia and a prophylactic antiemetic of 4 mg of IV ondansetron, and randomized to receive IPA or promethazine for treatment of breakthrough PONV Demographics, verbal numeric rating scale (VNRS) scores for nausea, time to 50% reduction in VNRS scores, and overall antiemetic and incidence of PONV were measured. The data for 85 subjects were included in analysis; no differences in demographic variables or baseline measurements were noted between groups. The IPA group reported a faster time to 50% reduction in VNRS scores and decreased overall antiemetic requirements. A similar incidence in PONV was noted between groups. Based on these findings, we recommend that inhalation of 70% IPA is an option for treatment of PONV in high-risk patients who have received prophylactic ondansetron.", "To evaluate whether isopropyl alcohol vapor is an effective treatment for postoperative nausea and vomiting.\n Double-blind, randomized, controlled study.\n Pediatric surgery center.\n 91 ASA physical status I and II children age 6-16 years, scheduled to undergo general anesthesia and elective outpatient surgery.\n Subjects were randomized to inhale isopropyl alcohol or saline. The intervention was repeated up to three times. If postoperative nausea or vomiting persisted after three sequences, intravenous ondansetron was administered as rescue therapy.\n Improvement in nausea was assessed using a visual analog scale, and improvement in vomiting was assessed using categorical analysis. After three treatment sequences, 65% of the children in the treatment group and 26% of the children in the control group had a significant reduction in the severity of either nausea or vomiting (p = 0.03). However, 54% of subjects in the treatment group and 80% of subjects in the control group had recurrent nausea or vomiting within 20 to 60 minutes.\n Under the conditions of this study, repetitive inhaled isopropyl alcohol only achieved a transient antiemetic effect in children with established postoperative nausea or vomiting following general anesthesia and surgery.", "To determine whether aromatherapy can reduce postoperative nausea, the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU. After indicating the severity of nausea on a 100-mm visual analogue scale (VAS), subjects received randomized aromatherapy with isopropyl alcohol, oil of peppermint, or saline (placebo). The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients' nostrils and exhaled slowly through the mouth. Two and 5 minutes later, the subjects rated their nausea on the VAS. Overall nausea scores decreased from 60.6 +/- 4.3 mm (mean +/- SE) before aromatherapy to 43.1 +/- 4.9 mm 2 minutes after aromatherapy (P <.005), and to 28.0 +/- 4.6 mm 5 minutes after aromatherapy (P < 10(-6)). Nausea scores did not differ between the treatments at any time. Only 52% of the patients required conventional intravenous (IV) antiemetic therapy during their PACU stay. Overall satisfaction with postoperative nausea management was 86.9 +/- 4.1 mm and was independent of the treatment group. Aromatherapy effectively reduced the perceived severity of postoperative nausea. The fact that a saline \"placebo\" was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled.", "We compared the efficacy of inhaled isopropyl alcohol (IPA) with ondansetron for the control of postoperative nausea and vomiting (PONV) during a 24-hour period in 100 ASA class I-III women undergoing laparoscopic surgery. Nausea was measured postoperatively using a 0 to 10 verbal numeric rating scale (VNRS). The control group received ondansetron, 4 mg intravenously, and the experimental group inhaled IPA vapors. Breakthrough PONV was treated with 25-mg promethazine suppositories. Demographic and anesthesia characteristics were similar between groups. There was a significant difference between groups in mean +/- SD time to alleviation of PONV symptoms: for a 50% reduction in VNRS scores, 15.00 +/- 10.6 vs. 33.88 +/- 23.2 minutes was required in the experimental vs. the control group (P = .001). A total of 21 subjects (10 control; 11 experimental) reported PONV symptoms following discharge to home. The IPA treatment was successful in alleviating PONV symptoms in the home in 91% of the experimental group. We determined that using IPA after discharge from the postanesthesia care unit is a valuable method to control PONV in the hospital and at home. The results of this study suggest that IPA is much faster than ondansetron for 50% relief of nausea.", "Postoperative nausea, a common complication in patients receiving general anesthesia, was studied in this randomized investigation to compare the efficacy of 70% inhaled isopropyl alcohol and intravenous ondansetron. For the study, 100 healthy women, ASA physical status I or II, scheduled for outpatient gynecologic laparoscopic procedures randomly received 4 mg of intravenous ondansetron or isopropyl alcohol for the treatment of postoperative nausea. Nausea was measured on arrival to the postanesthesia care unit, at first complaint of nausea, every 5 minutes after initiation of therapy until nausea resolution, and every 15 minutes thereafter using a 0 to 10 verbal numerical rating scale. At 5, 10, and 15 minutes, the median verbal numerical rating scores between the ondansetron and alcohol groups were 6.00 and 3.00, 5.00 and 3.00, and 5.00 and 2.00, respectively (P = .002, .015, and .036, respectively). No statistically significant differences were found at any other time interval. Mean times from initiation of therapy to a 50% reduction in nausea between the ondansetron and alcohol groups were 6.3 minutes and 27.7 minutes, respectively (P = 0.022). Based on this study, it seems postoperative nausea can be resolved quicker using 70% inhaled isopropyl alcohol compared with intravenous ondansetron in women undergoing outpatient gynecologic laparoscopic procedures.", "This paper describes a research study to investigate the efficacy of peppermint oil as a treatment for postoperative nausea. It uses a three-condition experimental design using statistical analysis to compare groups. The Kruskal-Wallis test was used to establish significance and the Mann-Whitney test to differentiate significance between the groups. The control, placebo and experimental groups of gynaecological patients were compared, using variables known to affect postoperative nausea. They were found to be homogeneous for the purposes of the study. A statistically significant differences was demonstrated on the day of operation, using the Kruskal-Wallis test, P = 0.0487. Using the Mann-Whitney test the difference was shown to be between the placebo and experimental group (U = 3; P = 0.02). The experimental group also required less traditional antiemetics and received more opioid analgesia postoperatively. The total cost of the treatment was 48 pence per person." ]
"Isopropyl alcohol was more effective than saline placebo for reducing postoperative nausea and vomiting but less effective than standard anti-emetic drugs. There is currently no reliable evidence for the use of peppermint oil."
"CD001865"
[ "8998184", "12590989", "12173678", "17196358", "21149743", "16338740", "12394349", "8327418", "7707420", "11988381", "10564627", "8302104", "7563045", "16720537", "19105686", "12215248", "20978060", "18308500", "10391568", "18573775", "10564629", "16832795", "16916540", "19418107", "15749130", "20157016", "10160231", "16580059", "17627015", "12781927", "16377602", "9552998", "9388791", "16427245", "10358689", "21636633", "1949916", "8279610", "18190370", "21090893" ]
[ "Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing.", "Comparison of tailored interventions to increase mammography screening in nonadherent older women.", "Comparisons of tailored mammography interventions at two months postintervention.", "The effect of telephone versus print tailoring for mammography adherence.", "Electronic patient messages to promote colorectal cancer screening: a randomized controlled trial.", "Effects of breast cancer risk counseling for sexual minority women.", "Effects of risk counseling on interest in breast cancer genetic testing for lower risk women.", "A randomized trial of the impact of risk assessment and feedback on participation in mammography screening.", "Effects of individualized breast cancer risk counseling: a randomized trial.", "Effects of a mammography decision-making intervention at 12 and 24 months.", "Tailored risk notification for women with a family history of breast cancer.", "Strategies to increase mammography utilization.", "Effect of interventions on stage of mammography adoption.", "Effects of communicating social comparison information on risk perceptions for colorectal cancer.", "Mammography screening after risk-tailored messages: the women improving screening through education and risk assessment (WISER) randomized, controlled trial.", "Pre-counseling education materials for BRCA testing: does tailoring make a difference?", "A decision aid to support informed choices about bowel cancer screening among adults with low education: randomised controlled trial.", "A randomized trial of two print interventions to increase colon cancer screening among first-degree relatives.", "Adherence by African American men to prostate cancer education and early detection.", "Randomized trial of a self-administered decision aid for colorectal cancer screening.", "Cost-effectiveness comparison of five interventions to increase mammography screening.", "A randomized trial to improve early detection and prevention practices among siblings of melanoma patients.", "Effects of a telephone counseling intervention on sisters of young women with breast cancer.", "A randomized trial of generic versus tailored interventions to increase colorectal cancer screening among intermediate risk siblings.", "Increasing colorectal cancer screening among individuals in the carpentry trade: test of risk communication interventions.", "Effects of a mail and telephone intervention on breast health behaviors.", "Do tailored behavior change messages enhance the effectiveness of health risk appraisal? Results from a randomized trial.", "Impact of a multimedia intervention \"Skinsafe\" on patients' knowledge and protective behaviors.", "Effects of colon cancer risk counseling for first-degree relatives.", "Tailored messages for breast and cervical cancer screening of low-income and minority women using medical records data.", "The efficacy of tailored print materials in promoting colorectal cancer screening: results from a randomized trial involving callers to the National Cancer Institute's Cancer Information Service.", "Screening for hypercholesterolaemia in primary care: randomised controlled trial of postal questionnaire appraising risk of coronary heart disease.", "Encouraging underscreened women to have cervical cancer screening: the effectiveness of a computer strategy.", "Results of a randomized study of telephone versus in-person breast cancer risk counseling.", "A randomized trial of breast cancer risk counseling: the impact on self-reported mammography use.", "Effect of evidence based risk information on \"informed choice\" in colorectal cancer screening: randomised controlled trial.", "A randomized controlled trial to motivate worksite fecal occult blood testing.", "Physicians' recommendations for mammography: do tailored messages make a difference?", "Use of a decision aid for prenatal testing of fetal abnormalities to improve women's informed decision making: a cluster randomised controlled trial [ISRCTN22532458].", "Tailored versus generic interventions for skin cancer risk reduction for family members of melanoma patients." ]
[ "In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have yet to be determined.\n Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer.\n A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition (n = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served as a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests.\n The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P < .001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P < .01) and decreases in perceived benefits (P < .05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample.\n Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education may be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered.", "Recent increases in mammography use have led to a decrease in mortality from breast cancer.\n Building on the Health Belief Model, the Transtheoretical Model, and past effectiveness of tailored interventions, we conducted a prospective randomized trial (n = 773) to test the efficacy on mammography adherence of tailored interventions delivered by five different methods, i.e., telephone counseling, in-person counseling, physician letter, and combinations of telephone with letter and in-person with letter.\n All five interventions increased mammography adherence significantly relative to usual care (odds ratios, 1.93 to 3.55) at 6 months post intervention. The combination of in-person with physician letter was significantly more effective than telephone alone or letter alone. Women thinking about getting a mammogram at baseline were more likely to be adherent by 6 months; even those in usual care achieved 48% adherence compared with 50-70% in the intervention groups. In contrast, women not thinking about getting a mammogram needed the interventions to increase their adherence from 13% to over 30%.\n All five interventions were effective at increasing mammography adherence. Women not thinking about getting a mammogram were most likely to benefit from these tailored interventions while other women might need less intensive interventions.", "The recent decrease in breast cancer mortality has been linked in part to increased breast cancer screening. Although the percentage of women screened once is rising, rate of continued adherence is poor. The purpose of this article is to assess the effects of tailored mammography interventions implemented prospectively in a factorial design contrasting groups receiving either (a) usual care (no intervention), (b) tailored telephone counseling for mammography, (c) tailored mailed materials promoting mammography, or (d) a combination of tailored mail and telephone counseling. This prospective, randomized study with a 2 x 2 factorial design included women 51 years and older (N = 1,367) who were not adherent with mammography at baseline. The intervention is based on integration of the Transtheoretical and Health Belief Models. Participants were enrolled in one of two health maintenance organizations or seen in a university-related primary care clinic. Baseline data were collected on mammography history and beliefs and knowledge related to mammography. Data were collected via telephone interviews using previously developed scales. The follow-up interviewers were conducted with 976 women. The sample was 41% White, 56% African American, and 3% other. Mean age at baseline was 66.5. Logistic regression indicates that postintervention mammography status in all three intervention groups was significantly better than usual care, with odds ratios ranging from 1.66 (telephone only) to 2.16 (telephone plus mail).", "The purpose of this intervention was to increase mammography adherence in women who had not had a mammogram in the last 15 months.\n A prospective randomized intervention trial used four groups: (1) usual care, (2) tailored telephone counseling, (3) tailored print, (4) tailored telephone counseling and print. Participants included a total of 1244 women from two sites-a general medicine clinic setting serving predominately low-income clientele and a Health Maintenance Organization (HMO). Computer-tailored interventions addressed each woman's perceived risk of breast cancer, benefits and/or barriers and self-efficacy related to mammography screening comparing delivery by telephone and mail.\n Compared to usual care all intervention groups increased mammography adherence significantly (odds ratio 1.60-1.91) when the entire sample was included.\n All interventions groups demonstrated efficacy in increasing mammography adherence as compared to a usual care group. When the intervention analysis considered baseline stage, pre contemplators (women who did not intend to get a mammogram) did not significantly increase in mammography adherence as compared to usual care.\n Women who are in pre contemplation stage may need a more intensive intervention.", "Colorectal cancer is a leading cause of cancer mortality, yet effective screening tests are often underused. Electronic patient messages and personalized risk assessments delivered via an electronic personal health record could increase screening rates.\n We conducted a randomized controlled trial in 14 ambulatory health centers involving 1103 patients ranging in age from 50 to 75 years with an active electronic personal health record who were overdue for colorectal cancer screening. Patients were randomly assigned to receive a single electronic message highlighting overdue screening status with a link to a Web-based tool to assess their personal risk of colorectal cancer. The outcomes included colorectal cancer screening rates at 1 and 4 months.\n Screening rates were higher at 1 month for patients who received electronic messages than for those who did not (8.3% vs 0.2%, P < .001), but this difference was no longer significant at 4 months (15.8% vs 13.1%, P = .18). Of 552 patients randomized to receive the intervention, 296 (54%) viewed the message, and 47 (9%) used the Web-based risk assessment tool. Among 296 intervention patients who viewed the electronic message, risk tool users were more likely than nonusers to request screening examinations (17% vs 4%, P = .04) and to be screened (30% vs 15%, P = .06). One-fifth of patients (19%) using the risk assessment tool were estimated to have an above-average risk for colorectal cancer.\n Electronic messages to patients produce an initial increase in colorectal cancer screening rates, but this effect is not sustained over time.\n clinicaltrials.gov Identifier: NCT01032746.", "Sexual minority women (lesbian and bisexual) represent a vulnerable group regarding their breast health. The participants in this study were 150 women aged 18-74 recruited via public announcements in mainstream and sexual minority communities in the greater Seattle metropolitan area. Potential participants were recruited to participate in a randomized trial of a breast cancer risk counseling intervention for sexual minority women. The counseling intervention produced significant reductions in perceived risk of breast cancer, anxieties and fears about breast cancer at 6 and 24 months, and increases in breast screening rates at 24 months in the intervention arm, compared with the control arm participants. These data add to the growing body of knowledge on sexual minority women's health and point to areas of community action and future research.", "A randomized trial was conducted to test the effects of two counseling methods (genetic counseling and group counseling) against a control no-intervention condition on interest in genetic testing in lower risk women.\n After completing baseline surveys, women (N = 357) were randomized to one of three conditions: to receive individual genetic risk counseling, to receive a group psychosocial group counseling, or to serve as a control group. Participants completed follow-up questionnaires 6 months after randomization.\n All participants had some familial history of breast cancer, but none had a family history indicative of autosomal dominant genetic mutation. At baseline over three fourths of the sample judged themselves to be appropriate candidates for testing. By the end of the survey, two thirds (70%) of the women in the counseling group still judged themselves to be appropriate candidates for testing. Findings were similar for interest in genetic testing. Changes in beliefs about genetic testing (e.g., beliefs about potential stigma associated with testing) altered the effects of counseling.\n These results indicate that counseling can change interest in genetic testing only slightly and that changing women's beliefs about the properties of testing might be one mechanism of doing so.", "Although rates of mammography screening among women in the general population have been increasing they still fall short of national goals. This study evaluated the effects on rates of participation in mammography screening of obtaining risk factor information and providing general or personalized risk information through direct mailed correspondence.\n Women enrollees in a health maintenance organization (N = 2,076), age 50 and above, were randomized to one of the following four groups: (a) no risk factor questionnaire + generic invitation, (b) no risk factor questionnaire + general risk invitation, (c) risk factor questionnaire + general risk invitation, and (d) risk factor questionnaire + personal risk invitation. Computerized visit records were monitored for 12 months following a mailed invitation to assess whether a mammogram had been obtained.\n Overall participation was 37.5% and the rate of participation did not differ significantly across groups (P = 0.26). Participation was related to age (P < 0.02), with rates highest for women ages 60-69 years (42.7%) compared with those for women ages 50-59 (35.5%) and those age 70+ (33.7%). Among women with a family history of breast cancer, the personalized risk invitation was associated with significantly higher participation compared with general risk invitation (66.7 versus 42.9%, respectively; P < 0.003).\n Women with a family history of breast cancer are more likely to obtain a mammogram if that fact is reinforced as a risk factor. Research on environmental barriers to mammography screening may suggest alternative strategies for increasing participation.", "Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety. In response to the need to communicate more accurate risk information to these women, specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States.\n Our purpose was 1) to evaluate the impact of a standardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2) to identify women most and least likely to benefit from such counseling.\n This study is a prospective randomized trial comparing individualized breast cancer risk counseling to general health counseling (control). We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative. Women with a personal history of cancer were excluded. Risk comprehension was assessed as the concordance between perceived \"subjective\" lifetime breast cancer risk and estimated \"objective\" lifetime risk.\n The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension, compared with women in the control condition (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.3-9.5; P = .01). However, in both groups, about two thirds of women continued to overestimate their lifetime risks substantially following counseling. Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line (P = .02). In addition, white women were less likely to benefit than African-American women (OR = 0.34; 95% CI = 0.11-0.99; P = .05).\n Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed.\n Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene, BRCA1 (and BRCA2 when that gene has also been cloned).", "Most women are not getting regular mammograms, and there is confusion about several mammography-related issues, including the age at which women should begin screening. Numerous groups have called for informed decision making about mammography, but few programs have resulted. Our research is intended to fill this gap.\n We conducted a randomized controlled trial, which ran from 1997 to 2000. Women aged 40 to 44 and 50 to 54, who were enrolled in Blue Cross Blue Shield of North Carolina, were randomly assigned to one of three groups: usual care (UC), tailored print (TP) materials, or TP plus tailored telephone counseling (TP+TC). We assessed the impact of tailored interventions on knowledge about breast cancer and mammography, accuracy of breast cancer risk perceptions, and use of mammography at two time points after intervention-12 and 24 months.\n At 12 and 24 months, women who received TP+TC had significantly greater knowledge and more accurate breast cancer risk perceptions. Compared to UC, they were 40% more likely to have had mammograms (odds ratio=0.9-2.1). The effect was primarily for women in their 50s. TP had significant effects for knowledge and accuracy, but women who received TP were less likely to have had mammography.\n Decision-making interventions, comprised of two tailored print interventions (booklet and newsletter), delivered a year apart, with or without two tailored telephone calls, significantly increased knowledge and accuracy of perceived breast cancer risk at 12 and 24 months post-intervention. The effect on mammography use was significant in bivariate relationships but had a much more modest impact in multivariate analyses.", "Evidence indicates that although first-degree relatives of breast cancer cases are at increased risk of developing the disease themselves, they may be underutilizing screening mammography. Therefore, interventions to increase the use of mammography in this group are urgently needed.\n A randomized two-group design was used to evaluate an intervention to increase mammography use among women (N = 901) with at least one first-degree relative with breast cancer. A statewide cancer registry was used to obtain a random sample of breast cancer cases who identified eligible relatives. The mailed intervention consisted of personalized risk notification and other theoretically driven materials tailored for high-risk women.\n An overall significant intervention effect was observed (8% intervention group advantage) in mammography at post-test. There was an interaction of the intervention with age such that there was no effect among women <50 years of age and a fairly large (20% advantage) effect among women 50+ and 65+. Health insurance, education, and having had a mammogram in the year before baseline assessment were positive predictors of mammography at post-test. Perceived risk, calculated risk, and relationship to index cancer case were not associated with mammography receipt.\n The intervention was successful in increasing mammography rates among high-risk women 50+ years of age. Further work is needed to determine why it was ineffective among younger women.\n Copyright 1999 American Health Foundation and Academic Press.", "This study compared the effects of theoretically driven interventions on compliance with mammography utilization. A 2 x 2 factorial design yielded four groups: a control group, a belief intervention group, an informational intervention group, and a belief/informational intervention group. A probability sample of 301 women, age 35 and older, without a history of breast cancer were randomly assigned to groups. Subjects in the intervention groups received individually tailored messages to alter beliefs or provider information related to mammography screening. Belief messages were developed from Health Belief Model constructs. Belief interventions significantly influenced all belief variables except perceived susceptibility in the desired direction. Women in the belief/informational intervention group were almost four times more likely than those in the control group to comply with mammography recommendations in the year following intervention (odds ratio = 3.75). In addition, belief variables and intervention significantly predicted mammography compliance 1 year postintervention.", "Mammography has been found significantly to impact mortality in women; however, compliance is still problematic. A theoretical model which combined Health Belief Model (HBM) constructs with stage of mammography adoption was used to investigate the effect of an individualized belief and/or informational intervention on mammography compliance. A control group and three intervention groups (belief, information, and belief and information) were used. A probability sample of 405 women ages 40-88 years without a prior history of breast cancer was randomly assigned to groups. Subjects in the intervention group received individually tailored messages to alter beliefs or provider information related to mammography screening. Women in the combined belief/information group were over two times more likely to have been compliant with mammography 1 year postintervention than those in the control. In addition, groups who received the belief intervention had significantly more women that went from a lower to a higher stage of mammography adoption.", "People typically believe their health risks are lower than those of others (i.e., optimistic bias). We sought to increase perceptions of colorectal cancer (CRC) risk among adults aged 50-75 who were nonadherent to fecal occult screening (FOBT). 160 participants were randomized to receive information about the following: (1) general CRC risk factors (control), (2) general and tailored CRC risk factor feedback (absolute risk group), or (3) absolute CRC risk factor feedback plus CRC feedback as to how their total number of risk factors compared with that of others (absolute plus comparative risk group). Primary outcomes were perceived absolute and comparative risks, attitudinal ambivalence toward FOBT, and screening intentions; the secondary outcome was return of a completed FOBT. Participants who were told that they had more than the average number of risk factors believed their comparative CRC risk was higher than that of controls and of participants informed that they did not have more than the average number of risk factors. Perceived absolute risk did not vary by group. Participants who received social comparison risk factor feedback expressed greater intentions to screen via a FOBT than participants who received absolute risk feedback and controls; they also expressed less ambivalence about FOBT screening than controls. Although not statistically significant, participants informed they were at lower comparative risk had the highest proportion of completing an FOBT than any other group. These results suggest that providing social comparison CRC risk factor feedback can effectively reduce optimistic comparative risk perceptions. Contrary to findings of models of health behavior change, being informed that one does not have more than the average number of CRC risk factors, while resulting in lower evaluations of perceived comparative risk, did not result in higher ambivalence toward and lower intentions to screen using FOBT or the lowest rate of screening.", "A randomized trial investigated the impact of risk-tailored messages on mammography in diverse women in the Virginia Commonwealth University Health System's gynecology clinics.\n From 2003 to 2005, 899 patients > or =40 years of age were randomized to receive risk-tailored information or general information about breast health. Multiple logistic regression analyses summarize their breast health practices at 18 months.\n At baseline, 576 (64%) women reported having a mammogram in the past year. At 18-month follow-up, mammography rates were 72.6% in the intervention group and 74.2% in the control group (N.S.). Women (n = 123) who reported worrying about breast cancer \"often\" or \"all the time\" had significantly higher mammography rates with the intervention (85.0%) vs. the controls (63.5%). No significant differences existed in clinical breast examination, self-examination, or mammography intentions between the two study arms. However, intervention women with lower education reported significantly fewer clinical breast examinations at follow-up.\n The brief intervention with a risk-tailored message did not have a significant effect overall on screening at 18 months. However, among those who worried, mammography rates in the intervention group were higher. Individual characteristics, such as worry about breast cancer and education status, may impact interventions to improve breast cancer prevention practices.", "Although tailored print materials (TPMs) have been assessed for a variety of behavioral targets, their effectiveness as decision aids for genetic testing had not been evaluated at the time this study began. We compared TPMs and non-tailored print material (NPMs) that included similar content about genetic testing for breast and ovarian cancer susceptibility. TPMs were prepared especially for an individual based on information from and about her. We mailed baseline surveys to 461 women referred by physicians or identified through a tumor registry. All had personal and family histories of breast and/or ovarian cancer and, on the basis of these histories, an estimated > or =10% probability of carrying a mutation in the breast/ovarian cancer genes BRCA1 or BRCA2. The 325 (70%) who responded were randomly assigned to receive TPM or NPM. Followup surveys, mailed 2 weeks following receipt of print materials, were returned by 262 women (81% of baseline responders). Participants were predominately white (94%) and well-educated (50% college graduates). The mean age was 49 years. At follow-up, TPM recipients exhibited significantly greater improvement in percent of correct responses for the 13-item true/false measure of knowledge (24% increase for TPM vs. 16% for NPM; p < 0.0001) and significantly less over-estimation of risk of being a mutation carrier (40% TPM group overestimated vs. 70% NPM; p < 0.0001). Anxiety did not differ significantly between groups. Reactions to materials differed on two items: \"seemed to be prepared just for me\" (76% TPM vs. 52% NPM; p < 0.001) and \"told me what I wanted to know about BRCA1 and 2 testing\" (98% TPM vs. 91% NPM; p < 0.05). TPMs showed an advantage in increasing knowledge and enhancing accuracy of perceived risk. Both are critical components of informed decision making.", "To determine whether a decision aid designed for adults with low education and literacy can support informed choice and involvement in decisions about screening for bowel cancer.\n Randomised controlled trial.\n Areas in New South Wales, Australia identified as socioeconomically disadvantaged (low education attainment, high unemployment, and unskilled occupations).\n 572 adults aged between 55 and 64 with low educational attainment, eligible for bowel cancer screening.\n Patient decision aid comprising a paper based interactive booklet (with and without a question prompt list) and a DVD, presenting quantitative risk information on the possible outcomes of screening using faecal occult blood testing compared with no testing. The control group received standard information developed for the Australian national bowel screening programme. All materials and a faecal occult blood test kit were posted directly to people's homes.\n Informed choice (adequate knowledge and consistency between attitudes and screening behaviour) and preferences for involvement in screening decisions.\n Participants who received the decision aid showed higher levels of knowledge than the controls; the mean score (maximum score 12) for the decision aid group was 6.50 (95% confidence interval 6.15 to 6.84) and for the control group was 4.10 (3.85 to 4.36; P<0.001). Attitudes towards screening were less positive in the decision aid group, with 51% of the participants expressing favourable attitudes compared with 65% of participants in the control group (14% difference, 95% confidence interval 5% to 23%; P=0.002). The participation rate for screening was reduced in the decision aid group: completion of faecal occult blood testing was 59% v 75% in the control group (16% difference, 8% to 24%; P=0.001). The decision aid increased the proportion of participants who made an informed choice, from 12% in the control group to 34% in the decision aid group (22% difference, 15% to 29%; P<0.001). More participants in the decision aid group had no decisional conflict about the screening decision compared with the controls (51% v 38%; P=0.02). The groups did not differ for general anxiety or worry about bowel cancer.\n Tailored decision support information can be effective in supporting informed choices and greater involvement in decisions about faecal occult blood testing among adults with low levels of education, without increasing anxiety or worry about developing bowel cancer. Using a decision aid to make an informed choice may, however, lead to lower uptake of screening. Trial registration ClinicalTrials.gov NCT00765869 and Australian New Zealand Clinical Trials Registry 12608000011381.", "First-degree relatives (FDRs) of people diagnosed with colorectal cancer (CRC) have a two- to threefold increased risk of developing the same disease. Tailored print interventions based on behavior change theories have demonstrated considerable promise in facilitating health-promoting behaviors. This study compared the impact of two mailed print interventions on CRC screening outcomes among FDRs.\n This randomized trial compared effects of two mailed print interventions--one tailored and one nontailored--on participation in CRC screening among FDRs of CRC survivors. Data collected via phone interviews from 140 FDRs at baseline, 1 week post-intervention, and 3 months post-intervention.\n At 3 months, both the tailored and nontailored interventions yielded modest but statistically insignificant increases in adherence to any CRC screening test (14% vs. 21%, respectively; p=0.30). While there were no main effects for tailored versus nontailored interventions, there were significant interactions that showed that the tailored print intervention had significantly greater effects on forward stage movement for CRC screening depending on stage of adoption at baseline, race, and objective CRC risk. Receipt of the tailored intervention was 2.5 times more likely to move baseline precontemplators and contemplators forward in stage of adoption for colonoscopy (95% CI: 1.10-5.68) and was three times more likely to move Caucasians forward in stage of adoption for FOBT (95% CI: 1.00-9.07). In addition, the tailored intervention was 7.7 times more likely to move people at average risk forward in stage of adoption for colonoscopy (95% CI: 1.25-47.75).\n The tailored print intervention was more effective at moving Caucasians, those in precontemplation and contemplation at baseline, and those at average risk forward in their stage of adoption for CRC screening.\n Both tailored and nontailored print interventions showed moderate effects for increasing CRC screening participation. Tailored print interventions may be more effective for certain subgroups.", "This study was designed to identify factors that predict adherence by African American men to prostate cancer education and early detection.\n In the spring of 1995, the authors identified 548 African American men who were patients at the University Health Services of the University of Chicago, were ages 40-70 years, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected from 413 men (75%). Participants were randomly assigned to either a minimal or an enhanced intervention group. Men in the former group were mailed a letter and a reminder that invited them to a urology clinic for prostate cancer education and early detection. Men in the enhanced intervention group were sent the same correspondence and were also given print material and telephone contacts, which were tailored to each recipient.\n Adherence was significantly higher (OR = 2.6, CI: 1.7-3.9) in the enhanced intervention group than in the minimal intervention group (51% and 29%, respectively). Men who were age 50 years or older (OR = 1.7, CI: 1.1-2.8), were married (OR = 1.8, CI: 1.2-2.9), believed that prostate cancer early detection examination should be performed in the absence of symptoms (OR = 2.3, CI: 1.3-4.0), and self-reported an intention to have an early detection examination (OR = 1.9, CI: 1.2-2.9) were also more likely to adhere.\n A tailored behavioral intervention can influence adherence to prostate cancer early detection among African American men. Individual background and cognitive and psychosocial characteristics may also affect behavior. Future studies should assess the impact of this type of intervention on cognitive and psychologic correlates of decision-making and behavior along the continuum of prostate cancer care. [See editorial on pages 1-2, this issue.]", "Previous studies have not assessed whether evidence-based information about the outcomes of colorectal cancer screening increases informed choice among people from a range of socioeconomic backgrounds nor have they assessed whether this can be administered away from a health-care provider.\n Randomized controlled trial in six primary care locations. Three hundred and fourteen people aged 50-74 years received a self-administered decision aid (DA) booklet about outcomes of biennial faecal occult blood testing (FOBT) screening or government consumer guidelines (G).\n Significantly more DA recipients (20.9%) were 'informed' compared with G recipients (5.8%) (P = 0.0001, OR 4.32; 95% CI 2.49 to 7.52); the DA did not affect values clarity (61.9% clear after DA versus 59.1% after G) nor screening decisions overall (87.3% would screen after DA versus 90.5% after G). Test uptake at one month was uniformly low (5.2% DA versus 6.6% G); mostly due to being 'too busy'. DA recipients were more likely to make decisions 'integrating' knowledge with values (10.4% DA versus 1.5% G). Decisions not to screen were equally uncommon in both groups but more likely to be uninformed in G (P = 0.03). More DA recipients from all education levels were 'informed' (P = 0.02), particularly in lower education (50.0% DA versus 17.8% G) and university-educated groups (79.4% DA versus 32.1% G).\n Detailed absolute risk and benefit information about FOBT screening can be effectively used at home by people to increase informed choice. The DA was effective in people with lower education levels.\n Unique Protocol ID 211705 ClinicalTrials.gov ID NCT 00148226.", "Mammography is the primary method used for breast cancer screening. However, compliance with recommended screening practices is still below acceptable levels. This study examined the cost-effectiveness of five combinations of physician recommendation and telephone or in-person individualized counseling strategies for increasing compliance with mammography.\n There were 808 participants who were randomly assigned to one of six groups. A logistic regression model with compliance as the dependent variable and group as the independent variable was used to test for significant differences and a ratio of cost to improvement in mammogram compliance evaluated the cost-effectiveness.\n Three of the interventions (in-person, telephone plus letter, and in-person plus letter) had significantly better compliance rates compared with the control, physician letter, or telephone alone. However, when considering costs, only one emerged as the superior strategy. The cost-effectiveness ratios for the five interventions show that telephone-plus-letter is the most cost-effective strategy, achieving a 35.6% mammography compliance at a marginal cost of 0.78 per 1% increase in women screened.\n A tailored phone prompt and physician reminder is an effective and economical intervention to increase mammography. Future research should confirm this finding and address its applicability to practice.\n Copyright 1999 American Health Foundation and Academic Press.", "Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction.\n We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently-diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: (1) an initial motivational and goal-setting telephone intervention session delivered by the health educator; (2) three sets of computer-generated materials specifically tailored to individual responses from the baseline survey; (3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and (4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened.\n 494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06-2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two-thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups.\n This study is the one of the first, to our knowledge, to address skin cancer risk-reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease.", "Women that have a first-degree relative diagnosed with breast cancer at an early age are at increased risk of the disease, yet they often lack information about their personal risk of breast cancer and early detection measures. An intervention to provide objective risk information, reduce worries, and promote screening and healthy behaviors was developed.\n In 1999-2002, a randomized pre-post design was used to test a tailored telephone counseling intervention with a sample of 163 women whose sisters were diagnosed with breast cancer at age 50 or younger in the San Francisco Bay Area. Participants were interviewed by telephone regarding their breast cancer risk factors, perceived risk, worries, lifestyle factors, and screening behavior. A modified Gail model was used to compute an objective measure of individualized lifetime risk.\n Risk overestimates averaged 25 percentage points. The intervention was effective in reducing overestimates in women age 50 and over but not in those under 50. The intervention was effective in increasing physical activity and reinforcing the conviction to maintain good breast health, but not in decreasing worries or increasing screening.\n Telephone counseling appears to be a viable tool for reducing risk overestimates and promoting healthy behaviors among sisters of women with breast cancer.", "Individuals with a sibling who has had colorectal cancer diagnosed before age 61 are at increased risk for colorectal cancer and may derive particular benefit from screening. Tailored interventions may increase participation in appropriate colorectal cancer screening.\n This study evaluated the efficacy of two tailored interventions and a generic print intervention.\n Participant siblings (N = 412) who were not up-to-date with colorectal cancer screening were randomly assigned to receive either a generic print pamphlet, a tailored print pamphlet, or a tailored print pamphlet and tailored counseling call. Colorectal cancer screening 6 months after the baseline interview was the outcome measure.\n Results indicated that colorectal cancer screening adherence increased among intermediate risk siblings enrolled in all three intervention groups. Participants in both tailored intervention groups reported having colorectal cancer screening at significantly higher rates than participants in the generic print group. The increase in colorectal cancer screening in the tailored print and counseling call group was not significantly higher than that achieved by the tailored print alone. Decisional balance partially mediated treatment effects. Tailored behavioral interventions are effective methods for increasing screening adherence but telephone counseling did not add significantly to treatment effects.", "Individuals in the carpentry trade, due to lifestyle habits and occupational exposures, may be at above-average risk for colorectal cancer (CRC). Based on the literature which suggests that increasing perceived risk motivates behavior change, we report on the effectiveness of four risk-communication interventions targeted to increase initial, yearly and repeat fecal occult screening (FOBT) among carpenters (N = 860) over a 3-year period.\n Our 2 x 2 factorial design intervention study varied two dimensions of providing CRC risk factor information: (1) type of risk factor-one set of interventions emphasized three basic risk factors (age, family history and polyps); the other set emphasized a comprehensive set of risk factors including basic, lifestyle, and occupational factors, and (2) tailoring/not tailoring risk factor information. Participants were provided FOBTs. Outcomes were the proportion of returned FOBTs.\n Varying the amount and intensity of delivering CRC risk factors information affected neither risk perceptions nor initial, yearly, or repeat screening. However, yearly and repeat screening rates were greater among participants who received interventions addressing comprehensive set of risk factors, especially with increasing age.\n Tailoring on several CRC risk factors appears insufficient to increase and sustain elevated perceptions of CRC risks to promote screening.", "This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer) or to a delayed treatment control group. Outcomes (mammography screening and quality of life) were measured at baseline in a telephone survey and again at a 12-month follow-up period. Women in the intervention group significantly increased screening mammography uptake by 12% and quality of life by 5.3 scale points compared to control participants. Changes in knowledge of breast cancer, genetic testing, and cancer worry all significantly predicted intervention changes. This successful intervention can help women make better breast health choices without causing increased worry.", "Health risk appraisal (HRA) remains one of the most widely used health promotion tools despite only equivocal evidence for its effectiveness. Theories of behavior change predict conventional HRA's ineffectiveness because risk information alone is seldom sufficient to change complex behaviors. In this study, a randomized trial compared the effects of feedback from an enhanced HRA with a typical HRA and a control group among adult patients from eight family medicine practices. The enhanced HRA assessed behavior-specific psychosocial factors and provided patients with computer-generated, individually-tailored behavior change information in addition to typical HRA risk feedback. Changes in seven behaviors were assessed at a 6 month follow-up. Overall, patients receiving enhanced HRA feedback were 18% more likely to change at least one risk behavior than were patients receiving typical HRA feedback or no feedback (OR = 1.18, 95% CI = 1.00, 1.39). The enhanced HRA feedback appeared to promote changes in cholesterol screening, dietary fat consumption and physical activity, but not in smoking, seat belt use, mammography and Pap smears. We conclude that the addition of theory-based, individually-tailored behavior change information may improve the effectiveness of HRA.", "Rates of malignant melanoma are rising, with those people with sun-sensitive skin most at risk. Health education interventions are needed to help people protect themselves by detecting early signs of melanoma and by protecting their skin from sunburn. This study aimed to evaluate the impact of an interactive multimedia intervention \"Skinsafe\" on patients' knowledge about melanoma and on their skin protective behaviors.\n In this cluster-randomized, controlled trial conducted in Nottinghamshire, UK, doctors and nurses in 5 family practices prescribed Skinsafe to patients with higher risk skin characteristics. Measures of melanoma knowledge, perceived risk of melanoma and reported skin protective behaviors were obtained at baseline and at 6-month follow-up from 259 patients receiving the intervention and 330 patients with higher risk skin characteristics in 5 matched control practices.\n Participants had low levels of melanoma knowledge at baseline. At follow-up, the intervention group had higher knowledge scores than control (3.71 vs. 3.03, P < or = 0.001), reported more protective skin behaviors (5.36 vs. 5.06, P = 0.007) and were more likely to report mole checking (odds ratio 1.67, 95% CI 1.04 to 2.70, P = 0.035). The Skinsafe intervention was evaluated positively by patients and could be used to support melanoma health education within clinical settings.", "Individuals with a first-degree relative who has had colorectal cancer are at increased risk for colorectal cancer and thus can benefit from early detection. Tailored risk counseling may increase adherence to screening guidelines in these persons. The present study evaluated a culturally sensitive Colon Cancer Risk Counseling (CCRC) intervention for relatives of colorectal cancer patients.\n A randomized trial evaluated personalized CCRC sessions with print materials and follow-up phone calls compared with a comparable General Health Counseling (GHC) intervention. One hundred and seventy-six siblings and children of colorectal cancer patients, living in Hawaii, were assessed at baseline and 4 and 12 months after intervention. Physician verification of colorectal cancer screening reports supplemented survey data.\n The CCRC intervention had a significant treatment effect at 4 months (13% greater increase than for GHC) that plateaued to a trend at 12 months. For those who were nonadherent at baseline, the CCRC led to a 17% net increase in screening adherence. Participants rated the CCRC intervention better than GHC for the amount and usefulness of new information.\n Using a study design that compared risk counseling to an attention-matched and tailored control condition provided a rigorous test of CCRC that emphasized the relevance of family experience with colorectal cancer. The combination face-to-face, phone, and small media risk counseling intervention for people with a family history of colorectal cancer should be considered for adoption in health care and public health settings.", "Barriers to screening and early detection often result in cancers in low-income and minority women diagnosed at stages too advanced for optimal treatment. This randomized controlled trial examined whether a personalized form (PF) letter containing generic cancer information and a personalized tailored (PT) letter containing minimally tailored individualized risk factor information based on medical records data affected breast and cervical cancer screening among 1574 urban low-income and minority women. The personalized form-letter group was significantly more likely to schedule a screening appointment and to have undergone a Pap test and mammography within 1 year after the intervention than were the tailored letter and control groups (P<0.001 for all comparisons). Personalized tailored letters that contain individualized cancer risk factor information may decrease the likelihood of receiving cancer screening among medically underserved low-income and minority women, but personalized form letters that contain generic cancer information may improve these rates in this disadvantaged population.", "In this large randomized trial among callers to the Cancer Information Service (CIS), tailored print materials were tested for efficacy in promoting colorectal cancer (CRC) screening (fecal occult blood test [FOBT], flexible sigmoidoscopy, or colonoscopy). All participants completed baseline interviews at the end of their usual service calls to the CIS, as well as short-term (6-month) and longer-term (14-month) telephone follow-up interviews. The study sample (n = 4,014) was restricted to English-speaking CIS callers 50 + years of age, who would be eligible for CRC screening at 14 months follow-up and did not call the CIS about CRC or CRC screening. Four experimental conditions were compared: a single untailored (SU) mailout of print material (the control condition); a single tailored (ST) mailout of print material; four (multiple) tailored (MT) mailouts of print materials spanning 12 months, all of which were tailored to information obtained at baseline; and four (multiple) retailored (MRT) mailouts also spanning 12 months, with retailoring of the print materials (mailouts 2, 3, and 4) based on updated information obtained from the 6-month follow-up interviews. Consistent with the main hypothesis of this trial, a significant linear trend across the SU, ST, MT, and MRT groups was found at 14 months (42%, 44%, 51%, and 48%, respectively, p = 0.05). Only for MT was there a significant difference compared with SU (p = 0.03) for the sample as a whole, while no differences were found for MT vs. MRT at 14 months. Significant moderator effects in the predicted direction were found among females, younger participants, and among those with a history of CRC screening, all of which involved the SU vs. MT MRT comparisons. Only among younger participants (ages 50-59) was there a difference between SU vs. ST at 14 months. Given these results, we conclude from this trial the following: (1) the MRT intervention failed to show added benefit beyond the MT intervention, (2) the significant intervention effects involving the MT and MRT conditions can be explained by tailoring and/or the longitudinal nature of both interventions, and (3) the most compelling evidence in support of tailoring was found for the ST condition among younger participants, where a significant need for interventions exists at the national level. Directions for future research are discussed in light of the results summarized above.", "To validate a self administered postal questionnaire appraising risk of coronary heart disease. To determine whether use of this questionnaire increased the percentage of people at high risk of coronary heart disease and decreased the percentage of people at low risk who had their cholesterol concentration measured.\n Validation was by review of medical records and clinical assessment. The questionnaire appraising risk of coronary heart disease encouraged those meeting criteria for cholesterol measurement to have a cholesterol test and was tested in a randomised controlled trial. The intervention group was sent the risk appraisal questionnaire with a health questionnaire that determined risk of coronary heart disease without identifying the risk factors as related to coronary heart disease; the control group was sent the health questionnaire alone.\n One capitation funded primary care practice in Canada with an enrolled patient population of about 12 000.\n Random sample of 100 participants in the intervention and control groups were included in the validation exercise. 5686 contactable patients aged 20 to 69 years who on the basis of practice records had not had a cholesterol test performed during the preceding 5 years were included in the randomised controlled trial. 2837 were in the intervention group and 2849 were in the control group.\n Sensitivity and specificity of assessment of risk of coronary heart disease with risk appraisal questionnaire. Rate of cholesterol testing during three months of follow up.\n Sensitivity of questionnaire appraising coronary risk was 87.5% (95% confidence interval 73.2% to 95.8%) and specificity 91.7% (81.6% to 97.2%). Of the patients without pre-existing coronary heart disease who met predefined screening criteria based on risk, 45 out of 421 in the intervention group (10.7%) and 9 out of 504 in the control group (1.8%) had a cholesterol test performed during follow up (P<0.0001). Of the patients without a history of coronary heart disease who did not meet criteria for cholesterol testing, 30 out of 1128 in the intervention group (2.7%) and 18 out of 1099 in the control group (1.6%) had a cholesterol test (P=0.175). Of the patients with pre-existing coronary heart disease, 1 out of 15 in the intervention group (6.7%) and 1 out of 23 in the control group (4.3%) were tested during follow up (P=0.851, one tailed Fisher's exact test).\n Although the questionnaire appraising coronary risk increased the percentage of people at high risk who obtained cholesterol testing, the effect was small. Most patients at risk who received the questionnaire did not respond by having a test.", "Computers that collect data from patients and provide both patients and practitioners with printed feedback on a range of health risks are a tool for assisting general practitioners with preventive care. This study assessed the impact of computer-generated printed feedback on cervical screening among women who were underscreened for cervical cancer.\n Female attenders at two Australian general practices were randomly allocated to Experimental or Control groups. Women in both groups completed a health risk survey on a touch screen computer prior to their consultation. Those in the Experimental group received printed pages summarizing their results, including their eligibility for cervical screening and last Pap test, for themselves and their doctor. The number and proportion of underscreened women who had a Pap test in the 6 months after completing the computer survey, as determined by pathology records, were examined.\n Of the 679 participants, 139 were classified as underscreened on the basis of self-report (74 Experimental, 65 Control) and 272 on the basis of their pathology records (148 Experimental, 124 Control). Overall about one-third of women had a test in the 6-month period, and the differences between the groups were not significant for women overall (18-70 years) or for women 18-49 years. Among women 50-70 who were underscreened based on self-report, those receiving the printout were more likely to have a Pap test in the next 6 months (P < 0.05). This pattern was also evident, but did not reach statistical significance, for older women who were underscreened based on pathology records.\n We are unable to draw conclusions regarding the effectiveness of the computer system due to the modest proportions of women screened, the small numbers, and the fact that the computer survey may have created an intervention effect in the Control group. As the study suggests the computer system is acceptable to women and may be effective for encouraging screening among older women, further exploration of the system is desirable.", "Women of all risk levels have reported high interest in obtaining genetic testing for breast cancer risk. Breast cancer risk counseling may help women to learn about their risk and appropriate options of testing. This study measured the effects of an intervention in-person and by telephone, compared to a control group.\n Participants were 340 women, recruited through a network of primary care physicians. They received a baseline questionnaire in the mail, were randomized to one of the three study arms, and completed a follow-up survey 3 months later.\n Both types of counseling were very well received. The counseling decreased women's cancer worry, risk perceptions, and intentions to pursue genetic testing. There were similar effects for both in-person and telephone counseling.\n Genetic counseling can be used to inform women at all risk levels about their breast cancer risk.\n Breast cancer risk counseling can be done in-person and by telephone--thereby reaching women in remote areas.", "We evaluated the impact of individualized breast cancer risk counseling on mammography use among women at risk for breast cancer.\n Participants (n = 508) were randomized to the breast cancer risk counseling intervention or a general health education control intervention, and 85% completed follow-up.\n In multivariate modeling, a significant group-by-education interaction demonstrated that among less-educated participants, breast cancer risk counseling led to reduced mammography use. There was no intervention effect among the more-educated participants.\n These results suggest that standard breast cancer risk counseling could have an adverse impact on the health behaviors of less-educated women.", "To compare the effect of evidence based information on risk with that of standard information on informed choice in screening for colorectal cancer.\n Randomised controlled trial with 6 months' follow-up.\n German statutory health insurance scheme.\n 1577 insured people who were members of the target group for colorectal cancer screening (age 50-75, no history of colorectal cancer).\n Brochure with evidence based risk information on colorectal cancer screening and two optional interactive internet modules on risk and diagnostic tests; official information leaflet of the German colorectal cancer screening programme (control).\n The primary end point was \"informed choice,\" comprising \"knowledge,\" \"attitude,\" and \"combination of actual and planned uptake.\" Secondary outcomes were \"knowledge\" and \"combination of actual and planned uptake.\" Knowledge and attitude were assessed after 6 weeks and combination of actual and planned uptake of screening after 6 months.\n The response rate for return of both questionnaires was 92.4% (n = 1457). 345/785 (44.0%) participants in the intervention group made an informed choice, compared with 101/792 (12.8%) in the control group (difference 31.2%, 99% confidence interval 25.7% to 36.7%; P < 0.001). More intervention group participants had \"good knowledge\" (59.6% (n = 468) v 16.2% (128); difference 43.5%, 37.8% to 49.1%; P < 0.001). A \"positive attitude\" towards colorectal screening prevailed in both groups but was significantly lower in the intervention group (93.4% (733) v 96.5% (764); difference -3.1%, -5.9% to -0.3%; P<0.01). The intervention had no effect on the combination of actual and planned uptake (72.4% (568) v 72.9% (577); P = 0.87).\n Evidence based risk information on colorectal cancer screening increased informed choices and improved knowledge, with little change in attitudes. The intervention did not affect the combination of actual and planned uptake of screening. Trial registration Current Controlled Trials ISRCTN47105521.", "Colorectal cancer is second only to lung cancer as a cause of cancer death in the United States. Studies have shown that fecal occult blood (FOB) tests are effective in detecting colorectal cancer in its early stages. To increase the participation in the FOB test among the working population, a randomized controlled trial was conducted. A total 278 federal employees 40 years or older in Washington State were randomly divided into a intervention group which received a Colorectal Cancer Risk Appraisal and a control group which received a simple information letter. After three months a follow-up questionnaire was sent to all participants to measure the effectiveness of the intervention. As a result of the study, the intervention group had a 4.3% higher compliance rate with the FOB test during the three month follow-up period (p = .10). The largest effect of the intervention was on the employees' intention to get a FOB test within the next year (62.6% in the intervention group vs. 36.2% in the control group, OR = 3.18, p less than .001).", "Message tailoring, based on individual needs and circumstances, is commonly used to enhance face-to-face patient counseling. Only recently has individual tailoring become feasible for printed messages. This study sought to determine whether printed tailored recommendations addressing women's specific screening and risk status and perceptions about breast cancer and mammography are more effective than standardized printed recommendations.\n Computer-assisted telephone interviews were conducted with 435 women, aged 40 to 65 years, who had visited family practice groups within the previous 2 years. Subjects were randomly allocated to receive individually tailored or standardized mammography recommendation letters mailed from physicians to patients' homes. Follow-up interviews were conducted 8 months later.\n Tailored letter recipients were more likely to remember and to have read more of their letters than standardized version recipients. After controlling for baseline status, tailored letter receipt was associated with more favorable follow-up mammography status for women with incomes below26,000 and for Black women.\n Tailored messages are a more effective medium for physicians' mammography recommendations; tailoring may be especially important for women of low socioeconomic status.", "To evaluate the effectiveness of a decision aid for prenatal testing of fetal abnormalities compared with a pamphlet in supporting women's decision making.\n A cluster randomised controlled trial.\n Primary health care.\n Women in early pregnancy consulting a GP.\n GPs were randomised to provide women with either a decision aid or a pamphlet. The decision aid was a 24-page booklet designed using the Ottowa Decision Framework. The pamphlet was an existing resource available in the trial setting.\n Validated scales were used to measure the primary outcomes, informed choice and decisional conflict, and the secondary outcomes, anxiety, depression, attitudes to the pregnancy/fetus and acceptability of the resource. Outcomes were measured at 14 weeks of gestation from questionnaires that women completed and returned by post.\n Women in the intervention group were more likely to make an informed decision 76% (126/165) than those in the control group 65% (107/165) (adjusted OR 2.08; 95% CI 1.14-3.81). A greater proportion of women in the intervention group 88% (147/167) had a 'good' level of knowledge than those in the control group 72% (123/171) (adjusted OR 3.43; 95% CI 1.79-6.58). Mean (SD) decisional conflict scores were low in both groups, decision aid 1.71 (0.49), pamphlet 1.65 (0.55) (adjusted mean difference 0.10; 95% CI -0.02 to 0.22). There was no strong evidence of differences between the trial arms in the measures of psychological or acceptability outcomes.\n A tailored prenatal testing decision aid plays an important role in improving women's knowledge of first and second trimester screening tests and assisting them to make decisions about screening and diagnostic tests that are consistent with their values.", "Improving strategies for risk reduction among family members of patients with melanoma may reduce their risk for melanoma.\n To evaluate the effects of two behavioral interventions designed to improve the frequency of total cutaneous skin examination by a health provider (TCE), skin self-examination (SSE), and sun protection among first degree relatives of patients with melanoma; and to evaluate whether increased intentions, increased benefits, decreased barriers, and improved sunscreen self-efficacy mediated the effects of the tailored intervention, as compared with the generic intervention on TCE, SSE, or sun protection.\n Four hundred forty-three family members (56 parents, 248 siblings, 239 children) who were nonadherent with these practices were randomly assigned to either a generic (N = 218) or a tailored intervention (N = 225) which included 3 print mailings and 1 telephone session. Participants completed measures of TCE, SSE, and sun protections at baseline, 6 months, and 1 year, and measures of intentions, benefits, barriers, and self-efficacy at baseline and 6 months.\n Those enrolled in the tailored intervention had almost a twofold increased probability of having a TCE ( p < .0001). Treatment effects in favor of the tailored intervention were also noted for sun protection habits ( p < .02). Increases in TCE intentions mediated the tailored intervention's effects on TCE. Increases in sun protection intentions mediated effects of the tailored intervention's effect on sun protection.\n Tailored interventions may improve risk reduction practices among family members of patients with melanoma.\n © 2010 APA, all rights reserved." ]
"There is strong evidence from three trials that personalised risk estimates incorporated within communication interventions for screening programmes enhance informed choices. However the evidence for increasing the uptake of such screening tests with similar interventions is weak, and it is not clear if this increase is associated with informed choices. Studies included a diverse range of screening programmes. Therefore, data from this review do not allow us to draw conclusions about the best interventions to deliver personalised risk communication for enhancing informed decisions. The results are dominated by findings from the topic area of mammography and colorectal cancer. Caution is therefore required in generalising from these results, and particularly for clinical topics other than mammography and colorectal cancer screening."
"CD007070"
[ "15998750", "16770975", "1477566", "18758677", "19501658", "18311814", "16131290" ]
[ "A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia.", "Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial.", "Electroacupuncture in fibromyalgia: results of a controlled trial.", "A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia.", "Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs).", "Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia.", "Treatment of fibromyalgia with formula acupuncture: investigation of needle placement, needle stimulation, and treatment frequency." ]
[ "Fibromyalgia is a common chronic pain condition for which patients frequently use acupuncture.\n To determine whether acupuncture relieves pain in fibromyalgia.\n Randomized, sham-controlled trial in which participants, data collection staff, and data analysts were blinded to treatment group.\n Private acupuncture offices in the greater Seattle, Washington, metropolitan area.\n 100 adults with fibromyalgia.\n Twice-weekly treatment for 12 weeks with an acupuncture program that was specifically designed to treat fibromyalgia, or 1 of 3 sham acupuncture treatments: acupuncture for an unrelated condition, needle insertion at nonacupoint locations, or noninsertive simulated acupuncture.\n The primary outcome was subjective pain as measured by a 10-cm visual analogue scale ranging from 0 (no pain) to 10 (worst pain ever). Measurements were obtained at baseline; 1, 4, 8, and 12 weeks of treatment; and 3 and 6 months after completion of treatment. Participant blinding and adverse effects were ascertained by self-report. The primary outcomes were evaluated by pooling the 3 sham-control groups and comparing them with the group that received acupuncture to treat fibromyalgia.\n The mean subjective pain rating among patients who received acupuncture for fibromyalgia did not differ from that in the pooled sham acupuncture group (mean between-group difference, 0.5 cm [95% CI, -0.3 cm to 1.2 cm]). Participant blinding was adequate throughout the trial, and no serious adverse effects were noted.\n A prescription of acupuncture at fixed points may differ from acupuncture administered in clinical settings, in which therapy is individualized and often combined with herbal supplementation and other adjunctive measures. A usual-care comparison group was not studied.\n Acupuncture was no better than sham acupuncture at relieving pain in fibromyalgia.", "To test the hypothesis that acupuncture improves symptoms of fibromyalgia.\n We conducted a prospective, partially blinded, controlled, randomized clinical trial of patients receiving true acupuncture compared with a control group of patients who received simulated acupuncture. All patients met American College of Rheumatology criteria for fibromyalgia and had tried conservative symptomatic treatments other than acupuncture. We measured symptoms with the Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory at baseline, immediately after treatment, and at 1 month and 7 months after treatment. The trial was conducted from May 28, 2002, to August 18, 2003.\n Fifty patients participated in the study: 25 in the acupuncture group and 25 in the control group. Total fibromyalgia symptoms, as measured by the FIQ, were significantly improved in the acupuncture group compared with the control group during the study period (P = .01). The largest difference in mean FIQ total scores was observed at 1 month (42.2 vs 34.8 in the control and acupuncture groups, respectively; P = .007). Fatigue and anxiety were the most significantly improved symptoms during the follow-up period. However, activity and physical function levels did not change. Acupuncture was well tolerated, with minimal adverse effects.\n This study paradigm allows for controlled and blinded clinical trials of acupuncture. We found that acupuncture significantly improved symptoms of fibromyalgia. Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety.", "To determine the efficacy of electroacupuncture in patients with fibromyalgia, a syndrome of unknown origin causing diffuse musculoskeletal pain.\n Three weeks' randomised study with blinded patients and evaluating physician.\n University divisions of physical medicine and rehabilitation and rheumatology, Geneva.\n 70 patients (54 women) referred to the division for fibromyalgia as defined by the American College of Rheumatology.\n Patients were randomised to electroacupuncture (n = 36) or a sham procedure (n = 34) by means of an electronic numbers generator.\n Pain threshold, number of analgesic tablets used, regional pain score, pain recorded on visual analogue scale, sleep quality, morning stiffness, and patient's and evaluating physician's appreciation.\n Seven of the eight outcome parameters showed a significant improvement in the active treatment group whereas none were improved in the sham treatment group. Differences between the groups were significant for five of the eight outcome measures after treatment.\n Electroacupuncture is effective in relieving symptoms of fibromyalgia. Its potential in long term management should now be studied.", "To evaluate the effectiveness of acupuncture for fibromyalgia.\n Fifty-eight women with fibromyalgia were allocated randomly to receive either acupuncture together with tricyclic antidepressants and exercise (n=34), or tricyclic antidepressants and exercise only (n=24). Patients rated their pain on a visual analogue scale. A blinded assessor evaluated both the mean pressure pain threshold value over all 18 fibromyalgia points and quality of life using SF-36.\n At the end of 20 sessions, patients who received acupuncture were significantly better than the control group in all measures of pain and in 5 of the SF-36 subscales. After 6 months, the acupuncture group was significantly better than the control group in numbers of tender points, mean pressure pain threshold at the 18 tender points and 3 subscales of SF-36. After one year, the acupuncture group showed significance in one subscale of the SF-36; at 2 years there were no significant differences in any outcome measures.\n Addition of acupuncture to usual treatments for fibromyalgia may be beneficial for pain and quality of life for 3 months after the end of treatment. Future research is needed to evaluate the specific effects of acupuncture for fibromyalgia.", "Controversy remains regarding the mechanisms of acupuncture analgesia. A prevailing theory, largely unproven in humans, is that it involves the activation of endogenous opioid antinociceptive systems and mu-opioid receptors (MORs). This is also a neurotransmitter system that mediates the effects of placebo-induced analgesia. This overlap in potential mechanisms may explain the lack of differentiation between traditional acupuncture and either non-traditional or sham acupuncture in multiple controlled clinical trials. We compared both short- and long-term effects of traditional Chinese acupuncture (TA) versus sham acupuncture (SA) treatment on in vivo MOR binding availability in chronic pain patients diagnosed with fibromyalgia (FM). Patients were randomized to receive either TA or SA treatment over the course of 4 weeks. Positron emission tomography (PET) with (11)C-carfentanil was performed once during the first treatment session and then repeated a month later following the eighth treatment. Acupuncture therapy evoked short-term increases in MOR binding potential, in multiple pain and sensory processing regions including the cingulate (dorsal and subgenual), insula, caudate, thalamus, and amygdala. Acupuncture therapy also evoked long-term increases in MOR binding potential in some of the same structures including the cingulate (dorsal and perigenual), caudate, and amygdala. These short- and long-term effects were absent in the sham group where small reductions were observed, an effect more consistent with previous placebo PET studies. Long-term increases in MOR BP following TA were also associated with greater reductions in clinical pain. These findings suggest that divergent MOR processes may mediate clinically relevant analgesic effects for acupuncture and sham acupuncture.", "Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM.\n Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Experimental pressure-evoked pain thresholds and clinical pain ratings (on the Short Form of the McGill Pain Questionnaire [SF-MPQ]) were also assessed prior to each imaging session\n Both experimental pain (P = 0.047 versus pretreatment) and SF-MPQ-rated clinical pain (P = 0.043 versus pretreatment) were reduced following treatment. Changes from pre- to posttreatment in Glu/Cr were negatively correlated with changes in experimental pain thresholds (r = -0.95, P < 0.001) and positively correlated with changes in clinical pain (r = 0.85, P = 0.002). Changes in the FMRI-determined blood oxygenation level-dependent effect (a measure of neural activation) were positively correlated with changes in Glu/Cr within the contralateral insula (r = 0.81, P = 0.002).\n Changes in Glu levels within the insula are associated with changes in multiple pain domains in patients with FM. Thus, H-MRS data may serve as a useful biomarker and surrogate end point for clinical trials of FM.", "The objective of this study was to investigate whether typical acupuncture methods such as needle placement, needle stimulation, and treatment frequency were important factors in fibromyalgia symptom improvement. DESIGN/SETTINGS/SUBJECTS: A single-site, single-blind, randomized trial of 114 participants diagnosed with fibromyalgia for at least 1 year was performed.\n Participants were randomized to one of four treatment groups: (1) T/S needles placed in traditional sites with manual needle stimulation (n = 29): (2) T/0 traditional needle location without stimulation (n = 30); (3) N/S needles inserted in nontraditional locations that were not thought to be acupuncture sites, with stimulation (n = 28); and (4) N/0 nontraditional needle location without stimulation (n = 2 7). All groups received treatment once weekly, followed by twice weekly, and finally three times weekly, for a total of 18 treatments. Each increase in frequency was separated by a 2-week washout period.\n Pain was assessed by a numerical rating scale, fatigue by the Multi-dimensional Fatigue Inventory, and physical function by the Short Form-36.\n Overall pain improvement was noted with 25%-35% of subjects having a clinically significant decrease in pain; however this was not dependent upon \"correct\" needle stimulation (t = 1.03; p = 0.307) or location (t = 0.76; p = 0.450). An overall dose effect of treatment was observed, with three sessions weekly providing more analgesia than sessions once weekly (t = 2.10; p = 0.039). Among treatment responders, improvements in pain, fatigue, and physical function were highly codependent (all p < or = 0.002).\n Although needle insertion led to analgesia and improvement in other somatic symptoms, correct needle location and stimulation were not crucial." ]
"There is low to moderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted."
"CD001087"
[ "9545998", "475542", "6578788", "16103032", "7953031" ]
[ "Randomized trial of general hospital and residential alternative care for patients with severe and persistent mental illness.", "A comparative trial of home and hospital psychiatric care. One-year follow-up.", "Psychiatric hospital versus community treatment: the results of a randomised trial.", "Randomised controlled trial of acute mental health care by a crisis resolution team: the north Islington crisis study.", "Home-based versus hospital-based care for people with serious mental illness." ]
[ "Severe and persistent mental illnesses are often lifelong and characterized by intermittent exacerbations requiring hospitalization. Providing needed care within budgetary constraints to this largely publicly subsidized population requires technologies that reduce costly inpatient episodes. The authors report a prospective randomized trial to test the clinical effectiveness of a model of acute residential alternative treatment for patients with persistent mental illness requiring hospital-level care.\n Patients enrolled in the Montgomery County, Md., public mental health system who experienced an illness exacerbation and were willing to accept voluntary treatment were randomly assigned to the acute psychiatric ward of a general hospital or a community residential alternative. There were no psychopathology-based exclusion criteria. Treatment episode symptom improvement, satisfaction, discharge status, and 6-month pre- and postepisode acute care utilization, psychosocial functioning, and patient satisfaction were assessed.\n Of 185 patients, 119 (64%) were successfully placed at their assigned treatment site. Case mix data indicated that patients treated in the hospital (N = 50) and the alternative (N = 69) were comparably ill. Treatment episode symptom reduction and patient satisfaction were comparable for the two settings. Nine (13%) of 69 patients randomly assigned to the alternative required transfer to a hospital unit; two (4%) of 50 patients randomly assigned to the hospital could not be stabilized and required transfer to another facility. Psychosocial functioning, satisfaction, and acute care use in the 6 months following admission were comparable for patients treated in the two settings and did not differ significantly from functioning before the acute episode.\n Hospitalization is a frequent and high-cost consequence of severe mental illness. For patients who do not require intensive general medical intervention and are willing to accept voluntary treatment, the alternative program model studied provides outcomes comparable to those of hospital care.", "The effectiveness of community-based treatment stressing home care was compared with hospital-based psychiatric care. One hundred and fifty-five patients destined for inpatient psychiatric care were randomly assigned to Home Care (76 patients) and to Hospital Care (79 patients). Symptoms, role functioning, and psychosocial burden on the family were similar at admission, one month, three months, six months, and one year. The mean in-hospital stay of Hospital Care patients was 41.7 days compared with a mean stay of 14.5 days for Home Care patients. The difference in the amount of ambulatory care received by patients in the two groups was not significant. The evidence is consistent: community-based psychiatric care is an effective alternative to hospital-based care for many but not all severely disabled patients. The active ingredients of successful community treatment are known, yet the lag in implementing these programs persists.", "One hundred and twenty patients presenting for admission were randomly allocated into two groups. Controls received standard hospital care and after-care. Projects were not admitted if this could be avoided; instead they and their relatives were provided with comprehensive community treatment and a 24-hour crisis service. Patients with a primary diagnosis of alcohol or drug dependence, organic brain disorder or mental retardation were excluded. During the 12 months study period, 96% of controls were admitted, 51% more than once. Of the projects, 60% were not admitted at all and only 8% were admitted more than once. Controls spent an average of 53.5 days in psychiatric hospitals; projects spent an average of 8.4 days. Community treatment did not increase the burden upon the community, was considered to be significantly more satisfactory and helpful by patients and their relatives, achieved a clinically superior outcome, and cost less than standard care and after-care.", "To evaluate the effectiveness of a crisis resolution team.\n Randomised controlled trial.\n 260 residents of the inner London Borough of Islington who were experiencing crises severe enough for hospital admission to be considered.\n Acute care including a 24 hour crisis resolution team (experimental group), compared with standard care from inpatient services and community mental health teams (control group).\n Hospital admission and patients' satisfaction.\n Patients in the experimental group were less likely to be admitted to hospital in the eight weeks after the crisis (odds ratio 0.19, 95% confidence interval 0.11 to 0.32), though compulsory admission was not significantly reduced. A difference of 1.6 points in the mean score on the client satisfaction questionnaire (CSQ-8) was not quite significant (P = 0.07), although it became so after adjustment for baseline characteristics (P = 0.002).\n Crisis resolution teams can reduce hospital admissions in mental health crises. They may also increase satisfaction in patients, but this was an equivocal finding.", "A controlled study tested whether the superior outcome of community care for serious mental illness (SMI) in Madison and in Sydney would also be found in inner London.\n Patients from an inner London catchment area who faced emergency admission for SMI (many were violent or suicidal) were randomised to 20 months or more of either home-based care (Daily Living Programme, DLP; n = 92), or standard in-patient and later out-patient care (controls, n = 97). Most DLP patients had brief in-patient stays at some time. Measures included number and duration of in-patient admissions, independent ratings of clinical and social function, and patients' and relatives' satisfaction.\n Outcome was superior with home-based care. Until month 20, DLP care improved symptoms and social adjustment slightly more, and enhanced patients' and relatives' satisfaction. From 3 to 18 months DLP care greatly reduced the number of in-patient bed days as long as the DLP team was responsible for any in-patient phase its patients had. Cost was less. DLP care did not reduce the number of admissions, nor of deaths from self-harm (3 DLP, 2 control). One DLP patient killed a child. Even at 20 months many DLP and control patients still had severe symptoms, poor social adjustment, no job, and need for assertive follow-up and heavy staff input. (Beyond 20 months most gains were lost apart from satisfaction.)\n It is unclear how much the gain until 20 months from home-based care was due to its site of care, its being problem-centred, its teaching of daily living skills, its assertive follow-up, the home care team's keeping responsibility for any in-patient phase, its coordination of total care (case management), or to other care components. Home-based care is hard to organise and vulnerable to many factors, and needs careful training and clinical audit if gains are to be sustained." ]
"Care based on crisis intervention principles, with or without an ongoing home care package, appears to be a viable and acceptable way of treating people with serious mental illnesses. If this approach is to be widely implemented it would seem that more evaluative studies are still needed."
"CD000163"
[ "1988896", "2030849", "11423890", "8688397", "9492730", "15515998", "9740522", "8623871", "12212131" ]
[ "Peritoneal closure or non-closure at cesarean.", "A randomized study of closure of the peritoneum at cesarean delivery.", "A randomized controlled study of peritoneal closure at cesarean section.", "Nonclosure of the visceral and parietal peritoneum at caesarean section: a randomised controlled trial.", "Randomized study of non-closure of peritoneum in lower segment cesarean section.", "Closure vs non-closure of the visceral and parietal peritoneum at cesarean delivery: 16 year study.", "Closure versus non-closure of peritoneum at cesarean section--evaluation of pain. A randomized study.", "Closure or nonclosure of the visceral peritoneum at cesarean delivery.", "[Clinical analysis of 318 cases of new-mode cesarean section]." ]
[ "The value of peritoneal closure at the time of cesarean birth was evaluated prospectively. Two hundred forty-eight women undergoing low transverse cesarean through a Pfannenstiel skin incision were assigned to one of two groups: peritoneum open (N = 127) or peritoneum closed (N = 121). The mean (+/- SEM) surgical time in the open group (48.1 +/- 1.2 minutes) was significantly less than for the closed group (53.2 +/- 1.4 minutes) (P less than .005). There were no postoperative differences between the groups in the incidence of wound infection, dehiscence, endometritis, ileus, and length of hospital stay. Our study suggests that leaving the parietal peritoneum unsutured is an acceptable way to manage patients at cesarean delivery.", "This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure.", "To assess the benefits or problems that may be associated with peritoneal closure at cesarean section.\n A randomized-controlled study of women undergoing cesarean section in Sultan Qaboos University Hospital Maternity Unit. After the decision is taken for cesarean section, women were randomized to either repair of peritoneum using standard technique or non-repair of peritoneum. Duration of operation, maternal morbidity, blood loss assessed by post-operative hemoglobin change and requirement of transfusion, post operative infection, thromboembolic disease, and length of hospital stay were analyzed in 2 groups of patients. Sixty women were randomized into the study, 30 group A, had peritoneal closure and 30, group B, and had non-closure.\n The average duration of operation for group A was 61.9+/-12.734, and for group B was 53.56 +/-11.209 (p< 0.01 statistically significant). There was no statistically significant difference in the length of stay, estimated blood loss, the mean drop in hemoglobin, postoperative pyrexia, and wound infection rate between the 2 groups.\n Our study has confirmed the previous study findings, and has shown that there are no advantages in suturing of the peritoneum in terms of blood loss, blood transfusion, operation duration, postoperative pyrexia and wound infection. In fact non-suturing of the peritoneum was associated with shorter operation duration (p< 0.01 significant), and reduced cost.", "To assess the short term morbidity of nonclosure of the peritoneum at caesarean section.\n Women undergoing a lower segment caesarean section were randomly allocated to either closure or nonclosure of the visceral and parietal peritoneum.\n Tertiary Care University Hospital of Geneva.\n Length of post-operative hospital stay. Other outcomes include maternal pain as assessed by both a visual analogue scale and the amount of post-operative analgesics administered, post-operative ileus, and febrile morbidity. Operative time was recorded.\n We allocated 137 women to the nonclosure group and 143 to the closure group. Population characteristics were similar between groups. The mean length of hospital stay was 6.5 (SD 1.9) days for the nonclosure group and 6.8 (SD 2.2) days for the closure group (P = 0.21). No differences were found in the level of post-operative pain, the number of analgesic doses given, nor in the proportion with febrile morbidity. Post-operative ileus resolved later in the closure group (P = 0.006). The mean operative time was shorter by 6 min (P = 0.006) in the nonclosure group.\n Short term post-operative morbidity and maternal pain are not increased by a shorter and more simple surgical procedure in which the peritoneum is left unsutured.", "The advantages of non-closure of the visceral and parietal peritoneum at lower segment cesarean section seems to be evident but in the reports published so far, the number of patients studied has been relatively small and the follow-up periods short. It is obviously of value to reconfirm such important observation in several institutions and therefore, in 1991, we decided to study non-closure of the peritoneum in lower segment cesarean section in a large series of patients with long-term follow-up of at least one year.\n A prospective randomized study of 361 patients undergoing lower segment cesarean section in a University Affiliated Hospital, Al-Ain, United Arab Emirates. The operative technique was randomized to include either non-closure of both visceral and parietal peritoneum (study group, n = 179) or closure of both layers (control group, n = 182). Patients were followed up according to a study protocol. The nursing staff and the obstetricians responsible for data collection were unaware as to which of the two groups the patients belonged to. Student-t test and Chi-square test were used for statistical analysis of the results, where appropriate, with a p < 0.05 considered probability level to reflect significant differences.\n Postoperative febrile morbidity and wound infection were significantly lower in the study group as compared to the control group (p < 0.001 and p < 0.05 respectively). The incidence of wound dehiscence, urinary tract infection and the time to opening of the bowels postoperatively were similar in the two groups. In the non-closure group, the average operating time was significantly shorter by 7.9 minutes (p < 0.01) and the hospital stay was one day less (p < 0.01). There were no patients with late postoperative complications or readmissions during 2-5 years of follow-up that could be attributed to complications associated with lower segment cesarean section.\n Non-closure of the visceral and parietal peritoneum at lower segment cesarean section is associated with fewer postoperative complications, is more cost effective and is simpler than the traditional operative technique of closing both peritoneal layers.", "To determine whether non-closure of visceral and parietal peritoneum at LSCS has advantages over peritoneal closure with regard to postoperative complication and adhesions.\n Prospective randomized controlled trial.\n Paholpolpayuhasena Hospital, Kanchanaburi province, Thailand\n Three hundred and sixty full-term pregnant women undergoing first cesarean section were divided into 3 groups (N = 120). Group A: non-closure of both visceral and parietal peritoneum. Group B. non-closure of only visceral peritoneum. Group C: closure of both visceral and parietal peritoneum. Postoperative complications were compared. Adhesions were evaluated in 65 patients returning for a second LSCS and compared for severity of adhesions. The three groups were compared using statistical analysis.\n There was no significant statistical difference between group A and C, group B and C for postoperative complications or number of adhesion formation. However, adhesions in the closure group were more severe.\n Closure of visceral and parietal peritoneum has no benefit over non-closure of visceral peritoneum and non-closure of both visceral and parietal peritoneum at LSCS.", "To evaluate the effects of leaving the parietal peritoneum open at lower segment cesarean section (LSCS) measured by postoperative pain.\n A randomized, prospective and double-blind study.\n Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark.\n Forty women referred for an elective cesarean section were assigned to one of two groups: peritoneum open (n=21) or peritoneum closed (n=19).\n Pain was evaluated twice a day from the first to the fifth postoperative day by Visual Analog Scales.\n Postoperative pain. Other outcomes include usage of analgesics, bowel function, postoperative complications, and hospital stay.\n We found no overall difference in postoperative pain. A tendency to less pain was found in the non-closure group from the third postoperative day to the fifth postoperative day. No differences were found either in the incidence of postoperative complications, or the time to return of bowel function. Concerning opiate analgesics the non-closure group had a significantly higher use in the second postoperative 24-hour period, but in the remains of the registration period it was significantly lower. For oral analgesics no difference was found in the first 24-hour period, but in the remains of the period the non-closure group had a significantly lower use.\n The VAS-scales showed no difference in postoperative pain comparing closure to non-closure of the parietal peritoneum. However, the use of analgesics is lower in the non-closure group. We suggest leaving the parietal peritoneum open when performing LSCS.", "Our purpose was to determine whether nonclosure of the visceral peritoneum at low transverse cesarean delivery has advantages over suture peritonization with regard to postoperative morbidity.\n A prospective randomized trial of 549 women undergoing cesarean section was carried out; 262 were randomized to nonclosure and 287 to closure of the visceral peritoneum. Perioperative, intraoperative, and postoperative management decisions were made without reference to treatment groups. Statistical analysis compared intraoperative and postoperative outcome between the two groups.\n Operating and anesthesia times were significantly shorter in patients receiving nonclosure. The incidence of febrile morbidity and cystitis and the need for antibiotics and narcotics were all significantly greater when the peritoneum was closed. Hospital stay was significantly shorter after nonclosure.\n Nonclosure of the visceral peritoneum is associated with lower febrile and infectious morbidity. Routine closure of the visceral peritoneum should be abandoned at cesarean delivery.", "To study types of new mode cesarean section (CS) and its clinical value.\n Four hundred and sixty-eight pregnant women with operative indications were randomly divided into three groups: the new mode CS group whose peritoneum was not sewed, the new mode CS group whose peritoneum was sewed, and the lower segmental CS group. The duration of operation, bleeding volume, morbidity after operation, and B type ultrasound for examining the incision were observed.\n There were significant difference in the duration of operation, bleeding volume, and morbidity after operation between the lower segmental CS and the two types of the new mode CS (P < 0.05). There was no significant differences in the bleeding volume and morbidity after operation between the two types of the new mode CS (P > 0.05), but there were significant difference in the duration of operation and the incision examined by B type ultrasound (P < 0.05).\n The new mode CS has shorter operative period, less bleeding, weak pain, faster recovery of peristalsis, and lower incidence of post-operative morbidity." ]
"There was improved short-term postoperative outcome if the peritoneum was not closed. This in itself can support those who opt not to close the peritoneum. Long-term studies following caesarean section are limited; there is therefore no overall evidence for non-closure until long-term data become available. [Note: The 18 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]"
"CD009581"
[ "16454975" ]
[ "XS0601 reduces the incidence of restenosis: a prospective study of 335 patients undergoing percutaneous coronary intervention in China." ]
[ "XS0601, consisting of active ingredients (Chuangxiongol and paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention (PCI).\n A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery.\n A total of 308 patients (91.9%) completed the study and 145 cases (47.1%) received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs. (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs. 22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group (7.1% and 11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No significant side effects occurred within the 6-month follow-up period in the XS0601 group.\n Administration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients." ]
"The summary estimates indicate a protective effect of Xiongshao on restenosis and suggest that Xiongshao capsule may be used to prevent restenosis after a PCI procedure in CHD patients. However, this evidence is derived from small randomised trials, all conducted in China, and two of the included trials showed important methodological limitations that undermine the validity of the findings. Additional high-quality research trials with sufficient sample size are required."
"CD009270"
[ "3941934", "7413719", "351429" ]
[ "Anticonvulsant effect of cannabidiol.", "Chronic administration of cannabidiol to healthy volunteers and epileptic patients.", "Toward drugs derived from cannabis." ]
[ "nan", "In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 health human volunteers. Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting. Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals. In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups. Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo. The drugs were administered for along as 4 1/2 months. Clinical and laboratory examinations, EEG and ECG were performed at 15- or 30-day intervals. Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment, although these drugs no longer controlled the signs of the disease. All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination. 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient. The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved. The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed.", "Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants." ]
"No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy. The dose of 200 to 300 mg daily of cannabidiol was safely administered to small numbers of patients, for generally short periods of time, and so the safety of long term cannabidiol treatment cannot be reliably assessed."
"CD001213"
[ "8219661" ]
[ "A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile." ]
[ "Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis." ]
"There is currently no firm evidence on which to base treatment of acute guttate psoriasis. Studies comparing standard treatment modalities, including phototherapy and topical regimens, are required to enable informed decisions on treatment choices to be made."
"CD006842"
[ "10024754", "15635998", "7675553", "11093342", "11093341", "7478782", "12004158", "9792567", "16305267", "12556258", "9674466", "9701429", "19703826", "8905888", "11391327", "2390665", "11596162", "7809441", "10497374", "7921452", "14679493" ]
[ "Effects of the flutter device on pulmonary function studies among pediatric cystic fibrosis patients.", "Comparison of expectorated sputum after manual chest physical therapy and high-frequency chest compression.", "Short-term effects of three chest physiotherapy regimens in patients hospitalized for pulmonary exacerbations of cystic fibrosis: a cross-over randomized study.", "[Evaluation of autodrainage methods in a selected group of cystic fibrosis patients with home environment factors taken into consideration].", "[Evaluation of the efficiency of selected thoracic physiotherapy methods used in the treatment of patients with cystic fibrosis].", "Comparison of effects of an intrapulmonary percussive ventilator to standard aerosol and chest physiotherapy in treatment of cystic fibrosis.", "[Long-term evaluation of effectiveness for selected chest physiotherapy methods used in the treatment of cystic fibrosis].", "Comparison of the flutter device to standard chest physiotherapy in hospitalized patients with cystic fibrosis: a pilot study.", "Physiologic evidence for high-frequency chest wall oscillation and positive expiratory pressure breathing in hospitalized subjects with cystic fibrosis.", "A comparison of the therapeutic effectiveness of and preference for postural drainage and percussion, intrapulmonary percussive ventilation, and high-frequency chest wall compression in hospitalized cystic fibrosis patients.", "Sputum rheology changes in cystic fibrosis lung disease following two different types of physiotherapy: flutter vs autogenic drainage.", "Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis.", "Short-term comparative study of high frequency chest wall oscillation and European airway clearance techniques in patients with cystic fibrosis.", "A comparison of bronchial drainage treatments in cystic fibrosis.", "Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis.", "High-frequency chest compression system to aid in clearance of mucus from the lung.", "Comparison of high-frequency chest wall oscillation and oscillating positive expiratory pressure in the home management of cystic fibrosis: a pilot study.", "The Flutter VRP1 as an adjunct to chest physiotherapy in cystic fibrosis.", "Comparison of Flutter device and chest physical therapy in the treatment of cystic fibrosis pulmonary exacerbation.", "Comparison of high frequency chest compression and conventional chest physiotherapy in hospitalized patients with cystic fibrosis.", "Comparison of active cycle of breathing and high-frequency oscillation jacket in children with cystic fibrosis." ]
[ "Previous studies have shown that the Scandipharm Flutter airway clearance device has increased the ability of cystic fibrosis patients to expectorate mucus. Studies that show the effects of the Flutter on pulmonary function among the pediatric cystic fibrosis patients are limited. Thus, we embarked on a study to assess the device's effectiveness.\n The long-term effect of the Flutter on pulmonary function tests (PFTs) was studied and compared with other airway clearance techniques, such as chest physiotherapy (CPT) and Vital Signs, Inc. 9000 PEP positive expiratory pressure (PEP) therapy for cystic fibrosis patients of five to 17 years of age with mild to moderate disease. Of the 15 patients who qualified, six completed the study. The patients were evaluated using PFTs and a respiratory assessment at the beginning and end of each new therapy. Duration of each therapy was one month.\n No respiratory assessment parameters changed between the therapies studied. All patients who used the Flutter preferred it over the other two therapies. The patients stated they felt better clinically, were able to expectorate mucus more easily, and felt more in control of their therapies. Paired t-test statistical analysis from the PFT data indicated no significant changes in forced expiratory volume in the first second of expiration (FEV1), forced expiratory flow from 25 percent to 75 percent of the loop (FEF25-75), airway resistance (Raw), or specific airway conductance (sGaw) among the three therapies studied.\n This study has shown no significant change in respiratory assessment parameters or pulmonary function. Further studies involving multicenter trials are warranted to evaluate the effects of the Flutter on pulmonary function.", "This study is a quantitative comparison of the sputum produced by 12 subjects with cystic fibrosis (CF) who received high-frequency chest compression (HFCC) and standard chest physical therapy (CPT) in randomized order. Six subjects routinely used manual CPT and six routinely used the HFCC. None had acute infections or hospitalization in the six weeks before the study. Two certified respiratory therapists alternated subjects and CPT vs HFCC order during the two weeks of the matched study. For all sessions, the expectorated sputum was collected in preweighed cups, which were reweighed immediately after collection and again after evaporation to dryness. The wet and dry weights of the sputum produced as a result of the two techniques were significantly different, with HFCC having greater weight. Regardless of the mode of therapy, the sputum produced by the subjects who regularly received HFCC had greater water content than did the sputum produced by those subjects who regularly received CPT. No significant difference was found between the two therapists regarding sputum expectorated by the subjects during CPT. These results show that sputum production by subjects with CF who receive CPT by certified respiratory therapists can be as great as the sputum produced by the same subjects who receive HFCC. The results also suggest that unknown factors attributed to the therapists may produce different levels of effort from time to time that may decrease the respiratory therapists' effectiveness, whereas the HFCC therapy may be more consistently effective because it is entirely machine based.", "The aim of our study was to compare the short-term efficacy of three different chest physiotherapy (CPT) regimens (PD, postural drainage; PEP, positive expiratory pressure physiotherapy; HFCC, high-frequency chest compression physiotherapy) on patients with cystic fibrosis (CF) hospitalized for an acute pulmonary exacerbation. Sixteen patients with CF, 8 males, 8 females, aged 15-27 years (mean, 20.3 +/- 4), met the inclusion criteria: 1) age over 14 years; 2) mild or moderate airway obstruction; 3) sputum volume > 30 mL/day; 4) being proficient in PD and PEP CPT. Patients at admission had (mean +/- SD) forced volume in 1 second (FEV1) 52.2 +/- 21.9 percent predicted; Shwachman-Kulczycki clinical score 65.1 +/- 11 points; Chrispin-Norman chest radiography score 18.6 +/- 4.3 points. The three CPT regimens and a control-treatment (CONT) were administered in a random sequence, each patient receiving each treatment twice a day (in 50 minute sessions) for 2 consecutive days. During CONT and for 30 minutes after each session only spontaneous coughing was allowed. Wet and dry weight of sputum were recorded during the 50-minute sessions and 30 minutes afterward. Lung function was measured before and 30 minutes after each session. For each treatment a score was given by the patient for efficacy, and by both the patient and the physiotherapist for tolerance. Wet and dry weights of sputum collected during the sessions were greater for all CPT regimens than for CONT (P < 0.001, P < 0.0001). No significant differences between the three CPT regimens for both wet and dry weights were found when the number of coughs was taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of the study was an estimation of effectiveness of selected autodrainage methods used in the treatment of children with cystic fibrosis and an assessment of patients' preference in relation to investigated methods. We also estimated the patients and their families' relation to chest physiotherapy methods, which have been used at home for many years. We studied 17 patients, aged 10-18 (x 13.35), who were hospitalised in the Institute of Mother and Child Paediatric Clinical Dept. We compared four autodrainage methods: 1- force expiratory technique, 2- Flutter(R), 3- Flutter (R) with relaxation, 4- PEP system. Every investigated drainage methods were tested by each patient according to a determined procedure. The following indices were measured: weight of coughed up sputum, oxygen saturation (SaO2) before, during and after drainage, peak expiratory flaw (PEF) before and after drainage. Patients' relation to autodrainage methods was estimated on the ground of their subjective assessment in 0-5-point scale. The results showed that the force expiration technique and the Flutter(R) with relaxation are the most efficient autodrainage methods determined by their coughed up sputum weight. Patients using these methods coughed up x 1.36g and x 1.319 g sputum. Using Flutter(R) without relaxation, patients expectorated 1.199 g sputum. PEP system turned out the least effective. Patients using the PEP system coughed up x 0.87 g sputum. In comparison, patients using postural drainage with clapping expectorated x 0.63g sputum. We observed that the PEF decreased during every investigated drainage methods. There were no significant differences in SaO2 values before and after drainage. Concerning the patients' preference in relation to the investigated methods, patients appreciated the most force expiratory technique (68 points). The least appreciated was the PEP system (33 points). For comparison, postural drainage with clapping has been estimated at 48.87 points.", "In Poland the standard treatment of pulmonary manifestation of cystic fibrosis consists of physiotherapy techniques of postural drainage with clapping. However many studies demonstrated that various alternative airway clearance techniques performed in Europe the last few years have been more effective than postural drainage. The aim of the study was a comparative analysis of the efficiency of selected chest physiotherapy methods used in the treatment of children with cystic fibrosis. We studied 21 patients, aged 5-18 (x 10.57), who were hospitalised in the Paediatric Clinic of National Research Institute of Mother and Child in Warsaw, Poland. We compared five chest physiotherapy techniques: 1 - postural drainage with clapping, 2 - postural drainage with clapping and vibration, 3 - active cycle of breathing technique, 4 - Flutter(R), 5 - Flutter(R) with relaxation. Every investigated drainage method was tested by each patient according to a determined procedure. The following indices were measured: weight of coughed up sputum, oxygen saturation (SaO2) before, during and after drainage, peak expiratory flaw (PEF) before and after drainage. The biggest quantity of sputum determined by its coughed up weight was with active cycle of breathing technique (x 2.126 g). In comparison, in patients using postural drainage with clapping and clapping with vibration average sputum expectoration was 0.895 and 1.012 g. Flutter device is recommended for individual usage. Our findings demonstrate that the Flutter with relaxation effectively facilitates removal of mucus from airways (Flutter - x 1.48 g, Flutter with relaxation - x 2.012 g). We observed PEF decrease (p > 0.05) during postural drainage with clapping and vibration. There were no significant differences in SaO2 between the values before and after drainage in every investigated technique.", "Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis (CF). Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function. We have evaluated an intrapulmonary percussive ventilator (IPV), which is a device designed to enhance airway clearance and preserve lung function. A previous pilot study by us had determined that the device was acceptable to patients and is safe. We undertook a 6 month parallel comparative trial of the IPV versus standard, manual chest physiotherapy in 16 CF children and adults. No significant differences in spirometric measures, numbers of hospitalizations, use of oral or IV antibiotics, or anthropometric measurements were detected between the standard aerosol/chest physiotherapy group and the IPV group over the duration of the trial. Patient acceptance, as determined by participant survey, was good. The device appeared to be safe and durable. It was concluded that the IPV is as effective as standard aerosol and chest physiotherapy in preserving lung function and anthropometric measures, and there was no difference in the use of antibiotics and hospitalizations.", "The aim of this study was a long-term analysis of efficiency of selected chest physiotherapy methods used in the treatment of children with CF. We studied 80 CF children (39 male, 41 female), mean age ll.44yrs (range 6-18 yrs), with varying degree of severity. The study was carried out during 7 months. The subjects were assigned into four groups. Group had conventional postural drainage with clapping (33 patients, age x-11.12), group II- conventional postural drainage with clapping and vibration (16 patients, age x-11.25), group III - active cycle of breathing technique (18 patients, age x-10.5), group IV Flutter (13 patients, age x- 13.77). All patients had three physiotherapy sessions a day. We measured: FEV1 FVC, FEV1/FVC, MEF 25-7 %, PEF, before and after the study. In the group with postural drainage with clapping we observed statistically significant decrease of all studied parameters. The use of additional vibration improved FVC and FEV1/FVC values but the improvement was not statistically significant. FEV1, PEF and MEF 25 %, were significantly lower. Statistically significant increase of all studied parameters was observed in patients using ACBT. In the Flutter group we observed increase of FEV1 and FVC values. The other parameters were decreased without statistical significance. Analysis of variance of pulmonary function parameters between groups demonstrated significant differences in FEV1, PEF and MEF 50% between postural drainage with vibration and active cycle of breathing technique. Significant differences have also been shown in PEF between postural drainage with clapping and active cycle of breathing technique. We conclude that: 1) postural drainage with clapping is less effective compared with the other studied techniques.2) The use of additional vibration did not bring about improvement of drainage efficiency. Vibration increased airways resistance. 3) Flatter device may be less effective in peripheral airways clearance.", "A preliminary study comparing the efficacy and safety of the flutter device (Flutter) to standard, manual chest physiotherapy (CPT) in hospitalized cystic fibrosis (CF) patients undergoing an acute pulmonary exacerbation.\n Open label, comparative trial with alternate assignment.\n Community and childrens' hospital acute-care wards.\n Twenty-two CF patients (ages 8 to 44 years) undergoing a total of 33 hospitalizations for acute pulmonary exacerbation.\n Complete pulmonary function tests (PFTs) were done at baseline (admission), weekly, and upon discharge from the hospital. Clinical score (CS) was determined at the time of hospital admission and at discharge. Participants were assigned to receive supervised Flutter therapy or standard, manual CPT four times per day during the hospitalization. Patients were monitored for complications, including hemoptysis, hypoxemia, and pneumothorax.\n The groups (CPT and Flutter) did not differ at baseline in demographics or Shwachman score, nor was length of hospitalization different. Significant improvements were noted from admission to discharge in CS and PFT results within each group. Mean percent change in CS and PFT results between CPT and Flutter groups showed no significant difference from hospital admission to discharge. Subsequent power analysis using the observed difference in percent change from admission to discharge for FEV1 indicated that to attain 80% power at alpha = 0.05, a sample of 219 subjects in each group would be necessary.\n Comparative trials of airway clearance techniques with sufficient sample size are lacking. Although the Flutter appears to be a useful device for independent, cost-effective, and safe administration of CPT in this pilot study, a much larger clinical trial would be necessary to make definitive conclusions.", "This investigation identified ventilation distribution, gas mixing, lung function, and arterial blood oxyhemoglobin saturation (SpO2) physiologic responses to 2 independent airway clearance treatments, high-frequency chest wall oscillation (HFCWO) and low positive expiratory pressure (PEP) breathing, for subjects who had cystic fibrosis (CF) and who were hospitalized during acute and subacute phases of a pulmonary exacerbation.\n Fifteen subjects with moderate to severe CF were included in this study.\n Subjects performed single-breath inert gas tests and spirometry before and immediately after HFCWO and PEP breathing at admission and discharge. Arterial blood oxyhemoglobin saturation was monitored throughout each treatment.\n At admission and discharge, PEP breathing increased SpO2 during treatment, whereas HFCWO decreased SpO2 during treatment. Ventilation distribution, gas mixing, and lung function improved after HFCWO or PEP breathing.\n High-frequency chest wall oscillation and PEP breathing are similarly efficacious in improving ventilation distribution, gas mixing, and pulmonary function in hospitalized people with CF. Because SpO2 decreases during HFCWO, people who have moderate to severe CF and who use HFCWO should have SpO2 monitored during an acute exacerbation.", "Cystic fibrosis (CF) patients have abnormally viscid bronchial secretions that cause airway obstruction, inflammation, and infection that leads to lung damage. To enhance airway clearance and reduce airway obstruction, daily bronchopulmonary hygiene therapy is considered essential.\n Compare the effectiveness of and patient preferences regarding 3 airway clearance methods: postural drainage and percussion (PD&P), intrapulmonary percussive ventilation (IPV), and high-frequency chest wall compression (HFCWC).\n The participants were hospitalized CF patients >or= 12 years old. Effectiveness was evaluated by measuring the wet and dry weights of sputum obtained with each method. In random order, each patient received 2 consecutive days of each therapy, delivered 3 times daily for 30 minutes. Sputum was collected during and for 15 minutes after each treatment, weighed wet, then dried and weighed again. Participants rated their preferences using a Likert-type scale. Mean weights and preferences were compared using analysis of variance with repeated measures. Patient preferences were compared using Freidman's test.\n Twenty-four patients were studied. The mean +/- SD wet sputum weights were 5.53 +/- 5.69 g with PD&P, 6.84 +/- 5.41 g with IPV, and 4.77 +/- 3.29 g with HFCWC. The mean wet sputum weights differed significantly (p = 0.035). Wet sputum weights from IPV were significantly greater than those from HFCWC (p < 0.05). The mean dry sputum weights were not significantly different. With regard to overall preference and to the subcomponents of preference, none of the 3 methods was preferred over the others.\n HFCWC and IPV are at least as effective as vigorous, professionally administered PD&P for hospitalized CF patients, and the 3 modalities were equally acceptable to them. A hospitalized CF patient should try each therapy and choose his or her preferred modality.", "The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device.\n To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer.\n No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.", "Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis.", "High frequency chest wall oscillation (HFCWO) is standard treatment for airway clearance in the USA and has recently been introduced in the UK and Europe. There is little published research comparing HFCWO with airway clearance techniques (ACTs) frequently used in the UK and Europe. The aim of this study was to compare the short-term effects of HFCWO with usual ACTs in patients with cystic fibrosis hospitalised with an infective pulmonary exacerbation.\n A 4-day randomised crossover design was used. Patients received either HFCWO on days 1 and 3 and usual ACTs on days 2 and 4 or vice versa. Wet weight of sputum, spirometry and oxygen saturation were measured. Perceived efficacy, comfort, incidence of urinary leakage and preference were assessed. Data were analysed by mixed model analysis.\n 29 patients (72% male) of mean (SD) age 29.4 (8.4) years and mean (SD) forced expiratory volume in 1 s (FEV(1)) percentage predicted (FEV(1)%) 38 (16.7) completed the study. Significantly more sputum was expectorated during a single treatment session and over a 24 h period (mean difference 4.4 g and 6.9 g, respectively) with usual ACTs than with HFCWO (p<0.001). No statistically significant change in FEV(1)% or oxygen saturation was observed after either HFCWO or usual ACTs compared with baseline. 17 patients (55%) expressed a preference for their usual ACT.\n During both a finite treatment period and over 24 h, less sputum was cleared using HFCWO than usual ACT. HFCWO does not appear to cause any adverse physiological effects and may influence adherence.", "We compared standard chest physical therapy and postural drainage (CPT/PD) with a new airway clearance therapy called high-frequency chest wall oscillation (HFCWO) in a group of stable cystic fibrosis (CF) patients. In this crossover trial, 29 CF patients (15 males, 14 females), aged 7-47 years that met the inclusion criteria were randomly assigned to alternate CPT/PD and HFCWO, on a daily basis, over a 4 day period. Each patient received 2 days of each form of therapy; treatment frequency and the length of treatment were the same for both techniques. Expectorated secretions were collected during each 30 minute therapy session and for 15 minutes following treatment. The wet and dry weights of collected secretions were determined gravimetrically, and the therapy methods were compared. Significantly more sputum was expectorated during HFCWO than during CPT/PD as determined by both the wet (P < 0.001) and the dry (P < 0.01) measurements. This study suggests that HFCWO is at least as effective as manual CPT/PD in clearing secretions from the airways in patients with cystic fibrosis.", "The objective was to evaluate the long-term effects of physiotherapy with an oscillating positive pressure device (\"flutter\") compared with physiotherapy with the use of a positive expiratory pressure (PEP) mask in patients with cystic fibrosis (CF). Study design: Forty children with CF were randomly assigned to performing physiotherapy with the PEP mask or the flutter device for 1 year. Clinical status, pulmonary function, and compliance were measured at regular intervals throughout the study.\n The flutter group demonstrated a greater mean annual rate of decline in forced vital capacity compared with the PEP group (-8.62 +/- 15.5 vs 0.06 +/- 7.9; P =.05) with a similar trend in forced expiratory volume in 1 second (-10.95 +/- 19.96 vs -1.24 +/- 9.9; P =.08). There was a significant decline in Huang scores (P =.05), increased hospitalizations (18 vs 5; P =.03), and antibiotic use in the flutter group.\n Flutter was not as effective in maintaining pulmonary function in this group of patients with CF compared with PEP and was more costly because of the increased number of hospitalizations and antibiotic use.", "The authors developed a high-frequency chest compression (HFCC) device to aid in mucous clearance for patients with obstructive lung disease. The device, designed for self-therapy, consists of a large-volume variable-frequency air-pulse delivery system and a nonstretchable inflatable vest worn by the patient. Pressure pulses are controlled by the patient and applied during expiration. Pulse frequency is tunable from 5 to 25 Hz. Maximum vest pressure is 39 mmHg (5.2 kPa), with patient-controlled vest inflation and deflation time constants of 0.5 s. Vest pressure increases from 28 mmHg (3.7 kPa) at 5 Hz to 39 mmHg (5.2 kPa) at 25 Hz. Preliminary clinical trials have shown the HFCC device to be more effective than standard chest physical therapy. The HFCC device yielded a mean volume of cleared mucus of 3.3 cc per session, compared with 1.8 cc for a conventional therapy session.", "Enhanced airway clearance is thought to result in better-maintained pulmonary function in cystic fibrosis (CF). Postural drainage, percussion, and vibration (PDPV) have been the primary airway clearance technique (ACT) employed in CF for over 40 years. Two new airway clearance modalities are high-frequency chest wall oscillation (HFCWO) and oscillating positive expiratory pressure (OPEP). This pilot study was undertaken to evaluate the efficacy of these techniques during home use, assess patient satisfaction with them as compared to PDPV, and assess the feasibility of performing a definitive comparative trial. The prospective, randomized, multicenter crossover trial was conducted at three urban academic CF Care Centers. Twenty-nine CF patients, 9-39 years of age, participated. Subjects performed 4 weeks each of HFCWO and OPEP following 2-week lead-in/washout periods. Spirometry, lung volumes, National Institutes of Health and Petty Scores, and a satisfaction survey were performed at baseline and after each treatment period. An ACT preference survey was completed at the conclusion of the study. Twenty-four subjects completed both therapies. There were no statistically significant differences between therapies for spirometry, lung volumes, or clinical scores. No significant safety issues arose during the study period. Compliance between therapies was similar. Significant differences among therapies existed in patient satisfaction. Given a choice of therapy, 50% of subjects chose HFCWO, 37% OPEP, and 13% PDPV. This study suggests that HFCWO and OPEP are safe and as effective as patients' routine therapies when used for airway clearance in a home setting. Patient satisfaction and preference differ among ACTs and should be considered when prescribing home therapy. A definitive, multi-center, comparative study evaluating long-term efficacy of these techniques is feasible.\n Copyright 2001 Wiley-Liss, Inc.", "The Flutter VRP1 (Flutter) is claimed to increase the clearance of excess bronchial secretions and to improve lung function and oxygenation, but these claims were based on computer models, laboratory assisted experiments and uncontrolled clinical trials. A prospective randomized clinical trial was undertaken, in subjects with cystic fibrosis, using the active cycle of breathing techniques as the 'gold standard'. The claims could not be substantiated and the possibility of sputum retention was of concern when the Flutter was used as significantly more sputum (P < 0.001) was cleared with the active cycle of breathing techniques alone. There were no significant changes in lung function or oxygenation.", "Chest physiotherapy (CPT) is recommended for the clearance of bronchial secretions in the management of patients with cystic fibrosis (CF). The Flutter valve (Scandipharm, Birmingham, AL) has been introduced as an alternative method to CPT for airway mucus clearance. The objective of this study was to compare the short-term effects of CPT and the Flutter valve on pulmonary function and exercise tolerance in patients with cystic fibrosis. Twenty-three patients, 5 to 21 years of age, were randomized to receive one of two interventions: CPT or the Flutter valve, upon admission to the hospital for a 2-week treatment of pulmonary exacerbation. Pulmonary function testing (PFTs) and the 6-min walk test were performed on admission, day 7, and day 14 of hospitalization. Data analysis indicated no significant differences between the two groups on admission. Both groups showed improvement in pulmonary function test results, but the Flutter group had a higher mean forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) compared to the CPT group after 1 week of intervention. Both groups continued to improve during the 2-week intervention, with no significant difference in FVC or FEV(1) between groups by the end of 2 weeks. Mean forced expiratory flow rate between 25-75% of vital capacity (FEF(25-75)), 6-min walk distance, and resting arterial oxyhemoglobin saturation (SaO(2)) showed little change by day 7, but improved significantly (P< 0.05) by day 14 of hospitalization in both groups, with no significant difference between groups. This study demonstrated that patients using the Flutter device had better pulmonary function after 1 week of therapy and similar improvement in pulmonary function and exercise tolerance compared to CPT after 2 weeks of therapy, suggesting that Flutter valve therapy is an acceptable alternative to standard CPT during in-hospital care of patients with CF.\n Copyright 1999 Wiley-Liss, Inc.", "Clearance of bronchial secretions is essential in the management of cystic fibrosis (CF) patients admitted for acute pulmonary exacerbation. Conventional physiotherapy (CPT) is labor-intensive, time-consuming, expensive, and may not be available as frequently as desired during hospitalization. High frequency chest compression (HFCC), which uses an inflatable vest linked to an air-pulse delivery system, may offer an attractive alternative. To study this, we prospectively studied 50 CF patients admitted for acute pulmonary exacerbation who were randomly allocated to receive either HFCC or CPT three times a day. On admission, clinical status and pulmonary function tests (PFT) in the HFCC group were not significantly different from those measured in the CPT group. Significant improvements in clinical status and PFT were observed after 7 and 14 d of treatment, and were similar in the two study groups, leading to patient discharge after similar periods of hospitalization. We conclude that HFCC and CPT are equally safe and effective when used during acute pulmonary exacerbations in CF patients. We speculate that HFCC may provide an adequate alternative in management of CF patients in a hospital setting.", "High-frequency chest compressions (HFCC) have been suggested as an alternative to conventional chest physiotherapy to aid sputum clearance in patients with cystic fibrosis (CF). We aimed to compare the active cycle of breathing techniques (ACBT) with the Hayek Oscillator Cuirass, performing HFCC on secretion clearance in children with CF during an exacerbation. Ten children (7 males; median age, 14 years; range, 9-16) received either two supervised sessions using HFCC or two self-treatment ACBT sessions in random order on successive days. Baseline pulmonary function was similar prior to treatments. Sputum weight increased significantly with ACBT compared with HFCC during treatment (5.2 g vs. 1.1 g, P < 0.005, morning; 4.1 g vs. 0.7 g, P < 0.01, afternoon). Pulmonary function improved significantly after morning ACBT (forced vital capacity (FVC): 2.67 l to 2.76 l, P < 0.03; forced expiratory volume in 1 sec (FEV1): 1.59 l to 1.62 l, P < 0.03). Following afternoon ACBT, there was a significant increase in FVC (2.64 to 2.79, P < 0.02), but no significant change in FEV1. Pulmonary function did not change at any time following HFCC. Compared with ACBT, HFCC by Hayek Cuirass is not an effective airway clearance treatment modality for children with CF during an infective exacerbation.\n Copyright 2004 Wiley-Liss, Inc." ]
"There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy. More adequately-powered long-term randomised controlled trials are necessary."
"CD003651"
[ "12181464", "11273219" ]
[ "15 Month follow up of African children following vaginal cleansing with benzalkonium chloride of their HIV infected mothers during late pregnancy and delivery.", "Vaginal lavage with chlorhexidine during labour to reduce mother-to-child HIV transmission: clinical trial in Mombasa, Kenya." ]
[ "To study mother to child HIV-1 transmission (MTCT) and infant mortality following benzalkonium chloride (BC) disinfection.\n A randomised, double blind phase II placebo controlled trial. Women testing positive for HIV-1 infection in prenatal care units in Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso, from November 1996 to April 1997 were eligible, with their informed consent. Women self administered daily a vaginal suppository of 1% BC (53) or matched placebo (54) from 36 weeks of pregnancy, plus a single dose during labour. The neonate was bathed with 1% BC solution or placebo within 30 minutes after birth. MTCT rate was assessed based on repeated polymerase chain reaction (PCR) and serology results. For the present analysis, children were followed up to 15 months.\n A total of 107 women were enrolled. Of 103 eligible liveborn children, 23 were HIV infected, 75 uninfected, and five of indeterminate status. MTCT transmission rate was 24.2% overall (95% confidence interval (CI): 14.3% to 30.4%). On an intent to treat basis, the transmission rate did not differ between the two groups (23.5%, CI 13.8 to 38.5, in the BC group and 24.8%, CI 15.0 to 39.6, in the placebo group at 15 months). Similarly, there was no difference in mortality at 15 months (22.9%, CI 13.7 to 36.9, in the BC group and 16.5%, CI 9.0 to 29.4, in the placebo group).\n This analysis failed to suggest any benefit of BC disinfection on mother to child HIV transmission or perinatal and infant mortality.", "To evaluate the effect of vaginal lavage with diluted chlorhexidine on mother-to child transmission of HIV (MTCT) in a breastfeeding population.\n This prospective clinical trial was conducted in a governmental hospital in Mombasa, Kenya. On alternating weeks, women were allocated to non-intervention or to intervention consisting of vaginal lavage with 120 ml 0.2% chlorhexidine, later increased to 0.4%, repeated every 3 h from admission to delivery. Infants were tested for HIV by DNA polymerase chain reaction within 48 h and at 6 and 14 weeks of life.\n Enrolment and follow-up data were available for 297 and 309 HIV-positive women, respectively, in the non-lavage and the lavage groups. There was no evidence of a difference in intrapartum MTCT (17.2 versus 15.9%, OR 0.9, 95% CI 0.6-1.4) between the groups. Lavage solely before rupture of the membranes tended towards lower MTCT with chlorhexidine 0.2% (OR 0.6, 95% CI 0.3-1.1), and even more with chlorhexidine 0.4% (OR 0.1, 95% CI 0.0-0.9).\n The need remains for interventions reducing MTCT without HIV testing, often unavailable in countries with a high prevalence of HIV. Vaginal lavage with diluted chlorhexidine during delivery did not show a global effect on MTCT in our study. However, the data suggest that lavage before the membranes are ruptured might be associated with a reduction of MTCT, especially with higher concentrations of chlorhexidine." ]
"Currently, there is no evidence of an effect of vaginal disinfection on the risk of MTCT of HIV. Given its simplicity and low cost, there is need for a large well-designed and well-conducted randomised controlled trial to assess the additive effect of vaginal disinfection on the risk of MTCT of HIV in antiretroviral treated women."
"CD006745"
[ "9425919", "12889565", "15973099", "16009687" ]
[ "Prospective randomized controlled trial comparing percutaneous acetic acid injection and percutaneous ethanol injection for small hepatocellular carcinoma.", "Comparison of percutaneous acetic acid injection and percutaneous ethanol injection for hepatocellular carcinoma in cirrhotic patients: a prospective study.", "Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study.", "Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less." ]
[ "To assess whether ultrasound-guided percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC), 60 patients with one to four HCCs smaller than 3 cm were entered onto a randomized controlled trial. Thirty-one and 29 patients, respectively, were treated by percutaneous acetic acid injection using 50% acetic acid or by percutaneous ethanol injection using absolute ethanol. There were no significant differences in age, sex ratio, Child-Pugh class, size of tumors, or number of tumors between the two groups. When there was no evidence of viable HCC from biopsy, plain and helical dynamic computed tomography, or angiography, the treatment was considered successful and was discontinued. All original tumors were treated successfully by either therapy. However, 8% of 38 tumors treated with percutaneous acetic acid injection and 37% of 35 tumors treated with percutaneous ethanol injection developed a local recurrence (P < .001) during the follow-up periods of 29 +/- 8 months and 23 +/- 10 months, respectively. The 1- and 2-year survival rates were 100% and 92% in percutaneous acetic acid injection and 83% and 63% in percutaneous ethanol injection (P = .0017). A multivariate analysis of prognostic factors revealed that treatment was an independent predictor of survival. The risk ratio of percutaneous acetic acid injection versus percutaneous ethanol injection was 0.120 (range, 0.027-0.528; P = .0050). In conclusion, percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small HCC.", "Ultrasound-guided percutaneous ethanol injection (PEI) and percutaneous acetic acid injection (PAI) are effective in the treatment of hepatocellular carcinoma (HCC). We conducted a prospective study to compare the therapeutic efficacy of both these methods.\n Sixty-three patients were treated by PAI using 50% acetic acid and 62 by PEI using pure ethanol. There were no significant baseline differences in age, sex, Child-Pugh class, tumour size and number, or other clinico-biochemical parameters between the two groups.\n During a follow-up period of 24 +/- 9 (range 6-38) months, 19 (30%) of the PAI group and 21 (34%) of the PEI group died (P = 0.704). The 1- and 3-year survival rates were 84% and 51% for the PAI group and 81% and 46% for the PEI group (P = 0.651). The corresponding tumour recurrence rates were 51% and 74% for the PAI group, and 54% and 64% for the PEI group (P = 0.787). The treatment sessions were 3.9 +/- 1.6 and 6.2 +/- 2.3 for the PAI and PEI groups, respectively, in each treatment cycle (P = 0.008). A multivariate analysis using the Cox regression model revealed that ascites (relative risk (RR) 3.1, 95% confidence interval (CI) 1.5-6.3, P = 0.002), large (>3 cm) or multinodular HCCs (RR 2.4, 95% CI 1.1-5.4, P = 0.04), and development of tumour recurrence (RR 7.0, 95% CI 3.1-16.0, P < 0.001) were independent, poor prognostic factors in both groups.\n PAI and PEI are equally effective in the treatment of HCC. PAI has the advantage of fewer treatment sessions in each treatment course. Careful pretreatment patient selection may improve survival.", "To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy, 2 treatments that have not been evaluated with a prospective study.\n A total of 76 patients were randomly assigned to 2 groups based on treatment; all had one or 2 tumors with diameter </=3 cm, with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency.\n Follow-up ranged from 12 to 59 months. Among percutaneous injection patients, 18 had recurrence 1 to 37 months after treatment (true recurrence, 11; original safety margin inadequate, 3; limitation of imaging technology to detect tiny tumors, 4). Three injection therapy patients died of cancer 25, 37, and 57 months after treatment. For the surgical resection group, 15 had recurrence 2 to 54 months after treatment (true recurrence, 12; limitation of imaging, 2; neck metastasis, 1). Five resection patients died of cancer at 11, 20, 23, 26, and 52 months, respectively. By Cox regression model and Kaplan-Meier survival analysis, there is no statistical significance for recurrence and survival between treatment groups. However, tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate, and Child class B liver cirrhosis correlated with shorter survival.\n Percutaneous ethanol injection therapy appears to be as safe and effective as resection, and both treatments can be considered first-line options for small hepatocellular carcinoma.", "The aim of this study was to compare the outcomes of radiofrequency thermal ablation (RFTA), percutaneous ethanol injection (PEI), and percutaneous acetic acid injection (PAI) in the treatment of hepatocellular carcinoma (HCC).\n A total of 187 patients with HCCs of 3 cm or less were randomly assigned to RFTA (n = 62), PEI (n = 62), or PAI (n = 63). Tumour recurrence and survival rates were assessed.\n One, two, and three year local recurrence rates were 10%, 14%, and 14% in the RFTA group, 16%, 34%, and 34% in the PEI group, and 14%, 31%, and 31% in the PAI group (RFTA v PEI, p = 0.012; RFTA v PAI, p = 0.017). One, two, and three year survival rates were 93%, 81%, and 74% in the RFTA group, 88%, 66%, and 51% in the PEI group, and 90%, 67%, and 53% in the PAI group (RFTA v PEI, p = 0.031; RFTA v PAI, p = 0.038). One, two, and three year cancer free survival rates were 74%, 60%, and 43% in the RFTA group, 70%, 41%, and 21% in the PEI group, and 71%, 43%, and 23% in the PAI group (RFTA v PEI, p = 0.038; RFTA v PAI, p = 0.041). Tumour size, tumour differentiation, and treatment methods (RFTA v PEI and PAI) were significant factors for local recurrence, overall survival, and cancer free survival. Major complications occurred in 4.8% of patients (two with haemothorax, one gastric perforation) in the RFTA group and in none in two other groups (RFTA v PEI and PAI, p = 0.035).\n RFTA was superior to PEI and PAI with respect to local recurrence, overall survival, and cancer free survival rates, but RFTA also caused more major complications." ]
"PEI and PAI do not differ significantly regarding benefits and harms in patients with early HCC, but only a limited number of patients have been examined and the risk of bias was high in all trials. There is also insufficient evidence to determine whether PEI or segmental liver resection is more effective. While some data from the single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make an assessment impossible."
"CD000299"
[ "8150348", "7047267", "2007362", "8147352", "6363219" ]
[ "Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.", "Sulphadoxine-pyrimethamine therapy in Crohn's disease.", "Controlled trial of antimycobacterial therapy in Crohn's disease. Clofazimine versus placebo.", "Antimycobacterial therapy in Crohn's disease: results of a controlled, double-blind trial with a multiple antibiotic regimen.", "Controlled trial of rifampicin and ethambutol in Crohn's disease." ]
[ "One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.", "nan", "In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N = 25) or to steroids and matching placebo (N = 24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12; P = NS) with a fall in disease activity score from 10.5 +/- 4.4 to 3.3 +/- 3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6; P = NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy.", "Several recent reports have suggested an association of atypical mycobacteria with Crohn's disease.\n The goal of this double-blind, placebo-controlled trial was to determine the efficacy of treatment with antimycobacterial drugs in maintaining clinical remission and in reducing active inflammatory lesions.\n Forty patients (15 male) with refractory, steroid-dependent Crohn's disease were randomized to receive 2 months of tapering steroids plus either a 9-month regimen of ethambutol, clofazimine, dapsone and 1-day dose only of rifampicin (n = 22), or identical placebo.\n Three patients (two on active drug) were unable to discontinue steroids, and one patient on active drug was withdrawn for side effects during the first 2 months. Three of the remaining 19 patients on active drug relapsed during the study period, compared with 11 of 17 on placebo (log likelihood ratio = 4.6; p = 0.03). Another patient was withdrawn in remission at 5 months for anemia related to dapsone. Nine patients whose disease relapsed or persisted on placebo were crossed over to active drug; five achieved sustained remission, two failed, and two were withdrawn for side effects. Substantial endoscopic or radiologic healing did not occur.\n This study suggests that the treatment regimen with rifampicin, ethambutol, clofazimine, and dapsone is effective in relief of symptoms and maintenance of remission in some Crohn's disease patients.", "We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease." ]
"Anti-tuberculous therapy may be effective in maintaining remission in patients with Crohn's disease when remission has been induced with corticosteroids combined with anti-tuberculous therapy. However, the results which support this conclusion come from a subgroup of only two trials with small numbers of patients and should be interpreted with caution. Use of this therapy cannot be recommended on the basis of this evidence."
"CD007893"
[ "8948303", "8564089", "1677063", "7594425", "7589392", "3169499", "9832182", "1970370", "2193613", "3281603", "9468460", "2676910", "1986287", "10964582", "8215491", "8007592" ]
[ "Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: a double-blind placebo-controlled study.", "Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma.", "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.", "Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males.", "Treatment of steroid-dependent bronchial asthma with cyclosporin.", "Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis.", "Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans.", "Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis.", "Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.", "Cyclosporin in rheumatoid arthritis: a double blind, placebo controlled study in 52 patients.", "Cyclosporine-induced hypertension and decline in renal function in healthy volunteers.", "[Results of cyclosporin treatment of severe, chronic psoriasis vulgaris].", "Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial.", "Each administration of cyclosporin A enhances skin microvascular reactivity in renal transplant recipients.", "Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, double-blind, placebo-controlled study.", "Sequential effects of cyclosporine therapy on blood pressure, renal function and neurohormones." ]
[ "A double-blind, randomized comparison between parenteral gold therapy (PGT) and cyclosporin A (CyA) vs PGT and placebo during 6 months was performed in 40 RA patients experiencing a decreasing effect of ongoing PGT. Patients' overall assessment of health was the only efficacy variable significantly better in the CyA- and PGT-treated vs the placebo- and PGT-treated group. Higher blood pressure and more signs of renal impairment were found during the 6 months treatment in the former compared with the latter group. Six months after the end of the combination therapy, a higher potassium value in the CyA-treated group was the only difference. In conclusion, no effects additional to those expected with single-drug therapy or additional risks of side-effects of either drug were found when combining low-dose CyA with ongoing PGT in RA patients with long disease duration.", "Patients with severe asthma who require long-term oral corticosteroid therapy are at risk of unwanted effects. Several immunosuppressive drugs have been assessed as corticosteroid-sparing agents in chronic asthma. We previously showed that cyclosporin A (CsA) administered for 12 wk improved lung function in corticosteroid-dependent patients. We have now investigated the corticosteroid-sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39 corticosteroid-dependent asthmatic patients were randomized to receive CsA (19 patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk. Attempts were then made by a physician ignorant of the trial therapy to reduce their prednisolone dosages at 14-d intervals, provided that a patient's asthma remained stable or improved. Three patients receiving CsA had to be withdrawn from the study before they completed 12 wk of therapy. The remaining 16 patients achieved a statistically significant reduction in median daily prednisolone dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in the patients taking placebo (p = 0.043). This reduction was most pronounced during the last 12 wk of active therapy. In addition, morning peak expiratory flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active-treatment group but not in the placebo group (p = 0.026 between groups). Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia, were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as compared with placebo, allowed a significant reduction in oral corticosteroid dosages in patients with severe asthma, and also improved lung function.", "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.", "To elucidate the sequential mechanisms underlying cyclosporin-induced hypertension and nephrotoxicity.\n A study of healthy males over the first 9 days of drug ingestion to permit the detection of serial changes in renal function and blood pressure in a situation free from the confounding variables of concomitant disease or drugs.\n Double-blind, placebo-controlled, randomized crossover study with cyclosporin (5 mg/kg twice a day) or placebo. Blood pressure and urinary sodium excretion were measured each day, and glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured on days 1, 4, 7 and 9. Cholesterol, lipoprotein (a) and endothelin were measured on days 1 and 9.\n GFR decreased by 9% with cyclosporin and was significantly lower than with placebo on day 4 of therapy. ERPF fell by 24%. The fall in GFR correlated significantly with suppressed plasma renin activity (P < 0.0001). Cyclosporin-induced hypertension occurred in the absence of any change in urinary sodium output or in plasma endothelin. Cyclosporin did not affect lipoprotein (a) levels during 9 days of cyclosporin therapy.\n Cyclosporin-induced hypertension and renal vasoconstriction are well established after 9 days of cyclosporin 5 mg/kg twice a day. We found no evidence to implicate either circulating endothelin or renal sodium retention in the onset of cyclosporin-induced hypertension. Cyclosporin-induced renal vasoconstriction appeared to occur when the protective mechanism of plasma renin activity suppression became exhausted.", "The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.", "The purpose of this pilot study was to determine whether daily administration of cyclosporin A to symptomatic patients with primary biliary cirrhosis for 1 yr would lead to a significant and sustained improvement in liver enzyme abnormalities. Twelve adult patients (11 female, 1 male; aged 52.6 +/- 8.9 yr, mean +/- SD) with serologic and histologically defined primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. Cyclosporin A was administered at sufficient dosages to maintain serum radioimmunoassay trough levels between 100 and 200 ng/ml (starting dosage, 2.5 mg/kg.day). After 1 yr of therapy, significant changes from pretreatment values were seen only in recipients of cyclosporin A. These included a 37% decrease in mean serum alkaline phosphatase and a 43% decrease in gamma-glutamyltransferase (controls +3% and -14%, respectively). Mean serum bilirubin and albumin levels and prothrombin times remained unaltered in the two groups, as did the extent of inflammation and fibrosis and the histologic staging of liver biopsy specimens. Although mean serum creatinine levels increased by 51% in recipients of cyclosporin A (+2% in controls), there were no associated changes in diastolic blood pressure or creatinine clearance values. Other side effects including thrombocytopenia, hirsutism, headaches, tremor, and parasthesiae were common in the treated group but not of sufficient severity to warrant adjustment in the dosage or discontinuation of therapy. The observed changes in hepatic, renal, and hematologic tests tended to return to baseline after discontinuation of therapy. Two patients, both placebo recipients, died of liver failure during the study period. The results of this study indicate that in symptomatic primary biliary cirrhosis, cyclosporin A administration is associated with a significant improvement in cholestatic liver enzyme abnormalities that persists for the duration of therapy. A progressive rise in serum creatinine levels and a high incidence of side effects raise concerns regarding the long-term safety of this agent in primary biliary cirrhosis.", "The acute hemodynamic effect of cyclosporine in man is controversial. A randomized, double blind, placebo-controlled, cross-over study was undertaken to evaluate the effect of a single oral dose of cyclosporine (20 mg/kg body weight) on mean blood pressure (MBP), heart rate (HR), forearm blood flow (FBF), and vascular resistance (FVR) in 16 healthy adult subjects. Subjects were studied twice, with an intervening period of 2 weeks, before and after the administration of either cyclosporine or the vehicle olive oil. Blood pressure was measured on brachial and digital arteries. After 30 min of rest, basal measurements were obtained and individuals were randomly assigned to receive either cyclosporine or the vehicle, and the same measurements were repeated 2 h later. Mean whole blood levels of cyclosporine were 1542+/-387 ng/mL (range 1000 to 2550) 2 h after the administration of a single oral dose of cyclosporine. Cyclosporine did not cause any significant change in the hemodynamic parameters when compared with vehicle. Pre- and post-cyclosporine data were as follows (means +/-/SD): MBP (determined by Finapres on the digital artery), 92+/-10 v 95+/-11 mm Hg; HR, 66+/-10 v 68+/-11 beats/min; FBF, 3.90+/-1.3 v 3.8+/-1.8 mL/ 100 mL/min; and FVR, 28+/-9 v 33 +/-18 units, respectively. For the vehicle the results were: MBP, 94+/-9 v 94+/-9; HR, 67+/-9v 67 /-11; FBF, 3.3+/-1.6 v 3.2+/-2.0; FVR, 35+/-14 v 37+/-15, respectively. These figures did not differ from those obtained with the auscultatory method applied to the brachial artery among 10 selected subjects studied with Finapres. In conclusion, we found no evidence that at supratherapeutic doses cyclosporine causes acute increase in blood pressure or peripheral vasoconstriction in humans.", "144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.", "Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for \"time to sustained progression\" or on a composite score of \"activities of daily living.\" Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.", "The efficacy and safety of cyclosporin A (CyA) for patients with rheumatoid arthritis were assessed in a four month double blind, placebo controlled study using an initial dosage of 5 mg/kg daily. Six patients withdrew from the study (two in the placebo group because of inefficacy of treatment and four in the CyA group because of side effects). These six patients were considered therapeutic failures. At the end of the trial the study treatment was considered as good or very good by 14 out of the 26 CyA group patients and by only two out of the 26 placebo group patients. Moreover, in the CyA group significant improvement was observed in five of the seven clinical assessment criteria. Clinical improvement was correlated with a decrease in C reactive protein, alpha 1 glycoprotein levels, and platelet count but not with erythrocyte sedimentation rate or rheumatoid factor titres. Renal toxicity (13 cases) remained the major problem in the management of these patients. This study shows that CyA is effective in active rheumatoid arthritis but requires close monitoring for toxicity.", "To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.\n Eighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects.\n CsA increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect.\n It was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine.", "Controlled double-blind studies have demonstrated the efficacy of 14 mg/kg per day cyclosporin A (CsA) in patients with severe psoriasis. Recently a placebo-controlled double-blind randomized study confirmed that CsA therapy (mean dose 5.5 mg/kg/day improves psoriasis significantly. We have carried out a placebo-controlled, double-blind, randomized trial involving 12 patients suffering from severe psoriasis resistant to local therapy. Within 4 weeks, 5 mg/kg per day CsA resulted in 6 patients in a mean reduction of 72.5% of the PASI score, which differed significantly from the mean reduction of 18.1% in 6 patients receiving placebo. The most important side-effect was reversible hypertension in 1 patient. The preliminary results of a dose-finding study that started recently indicate that 1-3 mg/kg per day CsA results in a significant improvement in the patient's condition.", "Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects.\n In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding.\n The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin.\n Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.", "Both impaired and enhanced microvascular function have been described in humans on cyclosporin A (CsA) therapy. In the present study we investigated the acute microvascular effects of a single CsA administration in renal transplant recipients on maintenance CsA therapy. Fourteen renal transplant recipients, median age 48 years (range 24-63 years), transplanted 4-12 weeks earlier, were included in this placebo-controlled, double-blinded, crossover study. All recipients had stable renal function; median serum creatinine was 116 micromol/L (range 80-184 micromol/L). Immunosuppressive therapy consisted of CsA, prednisolone, and either azathioprine or mycophenolate. Microvascular function was assessed by laser Doppler flowmetry in combination with acetylcholine (endothelium dependent) stimulation and the postocclusive reactive hyperemia test. Measurements were performed before (control) and 2.5 h following administration of CsA (Neoral) or matching placebo and repeated with reversed medication after at least 6 days. Vasodilative responses to acetylcholine stimulation were significantly higher following CsA ingestion compared with placebo. The mean change in AUC(1.5) (area under the flux versus time curve) from control to 2.5 h was 100 +/-145 for CsA and -292 +/- 140 AU x min for placebo (P = 0.047, n = 10). The postocclusive hyperemic response AUC(rh) was also significantly higher following CsA intake (39 +/- 4 AU x min) compared to placebo (30 +/- 4 AU x min) (P = 0.006, n = 12). This study shows that each dose of CsA induces a transient increase in skin microvascular reactivity in renal transplant recipients. We speculate that this might be due to the potentiation of one or several endothelial-dependent compensatory vasodilative mechanisms in the microvascular bed.\n Copyright 2000 Academic Press.", "Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders.\n Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders (P < .001). Cyclosporine, but not placebo, significantly reduced formation of new pustules (P = .001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group.\n Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP.", "We have studied the sequential effects of cyclosporine during the first four days after its initiation in an effort to elucidate the primary and secondary events in the pathogenesis of cyclosporine induced nephrotoxicity and hypertension. Knowledge about the earliest effects of cyclosporine provides a more logical approach for devising therapeutic strategies to counteract nephrotoxicity and hypertension. On day 1, cyclosporine acutely increased systemic BP and decreased urine volume. Plasma renin activity was suppressed by day 2 and remained so thereafter. Renal sodium excretion was not affected until day 4 at which point a natriuresis occurred. Cyclosporine exerted a more marked antidiuretic effect on day 4 compared to day 1, which was augmented by a physiological infusion of vasopressin. Over the first four days of therapy, glomerular filtration rate and effective renal plasma flow were unchanged. Our data show that cyclosporine induced hypertension in the initial stages is not sodium dependent, and that changes in renal water handling were not dependent on alterations in the glomerular filtration rate or effective renal plasma flow. In fact, a natriuresis occurred which was most likely due to a combination of pressure natriuresis and angiotensin II suppression. The cyclosporine induced antidiuresis may indicate a distal nephron effect since cyclosporine augmented the antidiuretic effect of vasopressin, although vasopressin levels per se were not increased by cyclosporine alone." ]
"Cyclosporine statistically significantly increases blood pressure compared to placebo in a dose-related fashion. The magnitude of increase in blood pressure is clinically significant and increases the risk of stroke, myocardial infarction, heart failure and other adverse cardiovascular events associated with elevated BP. Consequently prescribers should try to find the lowest effective dose in all patients receiving cyclosporine chronically."
"CD000066"
[ "19793585", "3305229", "21742284", "18715434", "1609525" ]
[ "Prevention of striae gravidarum with cocoa butter cream.", "[Effectiveness of Alphastria cream in the prevention of pregnancy stretch marks (striae distensae). Results of a double-blind study].", "Effects of olive oil on striae gravidarum in the second trimester of pregnancy.", "Cocoa butter lotion for prevention of striae gravidarum: a double-blind, randomised and placebo-controlled trial.", "[Attempt of preventive treatment of striae gravidarum using preventive massage ointment administration]." ]
[ "To determine whether cocoa butter cream is effective in preventing striae gravidarum.\n This randomized, double-blind, placebo-controlled trial enrolled 300 pregnant women: 150 women received cocoa butter cream and 150 women received a placebo cream. The women were followed-up from 16 weeks of pregnancy to delivery to assess the development of striae gravidarum. Maternal height, weight, and abdominal girth were recorded at each visit. After delivery the placenta was weighed, and anthropometry and Apgar scores of the neonate were recorded.\n The 2 groups had similar clinical parameters at booking. Striae gravidarum developed in 44% of patients using cocoa butter cream compared with 55% of those using placebo; the difference was not significant (chi(2)=2.8, df(1), P=0.09). Striae gravidarum were more common among younger women and those with large neonates. However, no relationship was found between development of striae and body mass index.\n Cocoa butter cream does not prevent striae gravidarum. In Afro-Caribbean women, development of striae is related to young age of the mother and large neonates.", "nan", "This study was performed in order to determine the effects of olive oil on striae gravidarum (SG) occurring within the second trimester of pregnancy. The intervention group, applied olive oil on their abdominal skin area twice a day until the end of the study term. The control group did not use any oil. Striae occurred in 40% of women using olive oil whilst striae were noted to occur in 50% of the control group. There was no significant difference between the intervention and control groups. This study notes that the use of olive oil to the end of the second trimester in pregnancy was not effective in reducing the occurrence of striae gravidarum.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "To assess whether application of cocoa butter lotion reduces the development of striae gravidarum (SG).\n Multicentre, double-blind, randomised and placebo-controlled trial.\n Beirut and Tripoli, Lebanon.\n Nulliparous women presenting for prenatal care.\n Nulliparous women presenting in the first trimester were randomly assigned to receive a lotion containing cocoa butter or a placebo lotion. Women were instructed to apply the assigned lotion daily until delivery.\n The development of striae over the abdomen, breasts and thighs postpartum.\n Of 210 women enrolled, 175 (83%) completed the study. Ninety-one women received the study lotion and 84 received the placebo. There was no difference in the development of SG (45.1% versus 48.8%; P = 0.730) or the severity of SG between cases and controls. The results did not change when presence of stretch marks at enrolment or compliance with the regimen were taken into account.\n Topical application of a lotion containing cocoa butter does not appear to reduce the likelihood of developing striae gravidarum.", "Striae distensae are an appreciable cosmetic problem for many pregnant women. Preventive application of a water/oil massage cream was tested in a group of 24 gravidae (control group: 26 patients). In the untreated control group striae distensae were observed in two-thirds of the patients, whereas the prophylactically-treated gravidae showed development of striae in only one third of the group given the test preparation. Better results were obtained in women with a favourable constitutional predisposition than in patients with a tendency to overweight. The massage cream was well tolerated by all gravidae." ]
"We found no high-quality evidence to support the use of any of the topical preparations in the prevention of stretch marks during pregnancy. There is a clear need for robust, methodologically rigorous randomised trials involving larger sample sizes to evaluate the effects of topical preparations on the development of stretch marks in pregnancy. In addition, it is important that preparations commonly used by women to prevent and treat stretch marks are evaluated within the context of robust, methodologically rigorous and adequately powered randomised trials."
"CD009009"
[ "3711252", "4569090", "19664653", "3797397", "12100779", "1256483", "4723642", "3903732", "4669179", "9602398", "7112052", "594708", "3720755", "608798" ]
[ "Multiphasic Health Checkup Evaluation: a 16-year follow-up.", "Social research problems in studies involving multiphasic health testing.", "Five years of lifestyle intervention improved self-reported mental and physical health in a general population: the Inter99 study.", "Systematic risk factor screening and education: a community-wide approach to prevention of coronary heart disease.", "General health screenings to improve cardiovascular risk profiles: a randomized controlled trial in general practice with 5-year follow-up.", "A controlled trial of multiphasic screening.", "A study to evaluate the effectiveness of multiphasic screening in Yugoslavia.", "WHO European Collaborative Trial of multifactorial prevention of coronary heart disease.", "Impact of a screening programme in general practice: a randomized controlled trial.", "Effects of an assessment of needs for medical and social services on long-term mortality: a randomized controlled study.", "The influence of repeated health examinations on mortality in a prospective cohort study, with a comment on the autopsy frequency. The study of men born in 1913.", "Effects of a health screening on mortality and causes of death in middle-aged men. A prospective study from 1970 to 1974 of mean in Malmö, born 1914.", "The multifactor primary prevention trial in Göteborg, Sweden.", "A controlled trial of multiphasic screening in middle-age: results of the South-East London Screening Study. The South-East London Screening Study Group." ]
[ "The Multiphasic Health Checkup Evaluation Study, a long-term clinical trial, has been completed. A study group of 5156 men and women age 35-54 at entry was urged to have annual multiphasic health checkups (MHCs) for 16 years. A control group of 5557 comparable subjects was not so urged but was followed up in a comparable fashion. The mean and median number of MHCs per person were 6.8 and 6, respectively, in the study group and 2.8 and 1, respectively, in the control group. During 16 years the study group experienced a 30% reduction (p less than 0.05) in deaths from pre-specified \"potentially postponable\" causes, largely associated with lower death rates from colorectal cancer and hypertension. This reduction was most pronounced in the early years of the study. The two groups did not differ to a statistically significant degree in mortality from all other causes (84% of total mortality) or in total mortality. There was no difference in self-reported disability in the overall groups. In the setting of our prepaid health care plan where MHCs were already available on a voluntary basis, a program of urging middle-aged persons to undergo regular MHCs brought about a substantial reduction in mortality from preselected diseases.", "nan", "Self-reported health has been shown to predict mortality. We lack knowledge on whether a lifestyle intervention can improve self-reported mental and physical health in a general population.\n Inter99, Denmark (1999-2006) is a randomised population-based intervention study. We screened for ischemic heart disease and repeatedly offered advice and assistance to obtain a healthier lifestyle. Health related quality of life was measured by Short Form 12 (SF-12); completed by 9322 at baseline and 7719 at five-year follow-up. In linear mixed models we investigated the effect of the intervention on self-reported health over time.\n At baseline men had higher physical health-component scores (PCS) than women. Living with a partner, being employed, and being healthy was associated with high PCS. The mental health-component scores (MCS) showed the same socio-demographic differences, except that MCS increased with age. Significantly fewer participants in the intervention groups had decreased their PCS and MCS compared with the control group. Adjusted multilevel analyses confirmed that the intervention significantly improved physical- (p=0.008) and mental health (p<0.001) over time compared with the control group.\n Screening for ischemic heart disease and offering lifestyle intervention had a significantly beneficial effect on mental and physical self-reported health in the long term in a general population.", "Within a community-wide heart disease prevention effort, it was hypothesized that personalized risk factor screening and education would result in modified health behaviors and reduced risk factor levels for coronary heart disease. Adults from a population sample were randomized to a community-wide screening and education program or were excluded from that program for 1 year. At the end of that year, both groups were measured for risk factor levels and related health behaviors. Those who received the screening and education program had significantly lower risk factor levels and other evidence of health behavior change, including lower blood cholesterol (206.9 vs 211.5 mg/dl), lower diastolic blood pressure (68.7 vs 70.0 mm Hg), lower resting heart rate (71.4 vs 72.7 bpm), and increased selection of low-fat and low-sodium meals in local restaurants. These data suggest that systematic risk factor screening and education may result in lower population risk for coronary heart disease.", "To investigate the impact of general health screenings and discussions with general practitioners on the cardiovascular risk profile of a random population of patients.\n A population-based, randomized, controlled, 5-year follow-up trial conducted in a primary care setting.\n The study group consisted of 2000 patients, randomly selected middle-aged men and women aged 30 to 50 years from family practices in the district of Ebeltoft, Denmark. Of these patients, 1507 (75.4%) agreed to participate. Patients were randomized into (1) a control group who did not receive health screenings, (2) an intervention group that received 2 health screenings, (3) an intervention group that received both the 2 screenings and a 45-minute follow-up consultation annually with their general practitioner.\n Cardiovascular risk score (CRS), body mass index (BMI), blood pressure, serum cholesterol, carbon monoxide in expiratory air, and tobacco use.\n After 5 years, the CRS, BMI, and serum cholesterol levels were lower in the intervention groups compared with the control group. The improved outcome was greater in the baseline risk groups. The number of patients with elevated CRS in the intervention groups was approximately half the number of patients with elevated CRS in the control group. The difference was not a result of medication use. There was no difference between the group that received consultations after the screenings and the group that had health screenings alone.\n Health screenings reduced the CRS in the intervention groups. After 5 years of follow-up, the number of persons at elevated cardiovascular risk was about half that expected, based on the prevalence/proportion in a population not receiving the health checks (the control group). The impact of intervention was higher among at-risk individuals. Consultations about health did not appear to improve the cardiovascular profile of the study population.", "A clinical controlled trial was designed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes. Three strata comprising 574 families (lower-income group enrolled in health maintenance organization, lower-income not enrolled in such a project, and a middle-income group employed by a utility company) were interviewed to obtain information on utilization, morbidity, health status, and attitudes. Sixty percent of adults in each stratum were then screened. All families were interviewed again one year later. The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects. Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians. Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment.", "nan", "Results are reported from a trial of multifactorial prevention of coronary heart disease (CHD) in occupational groups, involving randomization of 66 factories to intervention and control (49,781 men ages 40 to 59) in the United Kingdom, Belgium, Italy, and Poland. Net average reductions in the intervention factors were 1.2% (plasma cholesterol), 8.9% (daily cigarettes), 0.4% (weight), 2% (systolic blood pressure), and 11% for a combined risk estimate. Reductions were larger in high-risk men (19% for the combined estimate). Red blood cell fatty acid profiles were substantially changed. There was a net overall reduction of 7.4% in fatal CHD and 2.7% in total deaths. Benefits were larger in centers achieving larger risk factor reductions, and in one country--Belgium--the net decreases in CHD incidence and total deaths were significant at the 5% level. Benefit was at least as great in men with established ECG abnormality. It is concluded that CHD risk in middle-aged men seems to be reducible by simple and cost-effective means.", "nan", "The aim of this study was to investigate the long-term effects of one general health screening on mortality.\n After stratification and randomization of a population of 450,000 inhabitants, two groups were formed, an intervention group of 3064 people and a control group of 29,122 people. From the National Cause of Death Register, data were collected as regards death and causes of deaths for 1970-1990.\n Multivariate analysis was used to correct for known confounders. We then found no differences between the groups regarding deaths from all causes, cardiovascular diseases, cancer or accidents and poisoning.\n One general health screening seems to have little, if any value in preventing fatal diseases.", "In the Study of Men Born in 1913 it was possible to investigate the influence of repeated health examinations on mortality in a prospective cohort study. On January 1, 1963, 1010 men in the experimental group and 1956 in the control group were alive. The experimental group took part in repeated examinations in 1963, 1967, 1973 and 1980. Overt diseases were treated accordingly. Newly detected hypertension was also treated. By the end of a 15-year-long observation period, the cumulative mortality in the experimental group (14.5%) was not significantly lower than that in the control group (15.7%). In the experimental group, 855 took part. The mortality was significantly higher in the non-participating group. The autopsy frequency decreased for in-hospital deaths but increased for deaths outside hospital during the study period.", "All men born in even-numbered months in 1914 and domiciled in Malmö were invited in 1969 to participate in an investigation regarding risk factors for cardiovascular disease. Individuals with a blood pressure of 165/110 and over were treated and a sub-sample of heavy smokers were later invited to take part in a quit-smoking project. During the following five year period total and cause-specific mortality in the examined group was compared with corresponding data for men born in uneven months in 1914. Mortality in the examined cohort was lower than among controls and differed significantly from that in the control group with regard to cardiovascular mortality.", "The effect of a multifactorial intervention programme on coronary heart disease (CHD), stroke incidence and total mortality was determined in a random sample of men, 47-55 years old at entry. The intervention group comprised 10 004 men, and the two control groups were of similar size. The intervention consisted of antihypertensive treatment in subjects with screening blood pressure above 175 mmHg systolic or 115 mmHg diastolic, dietary advice to men with serum cholesterol levels above 260 mg per 100 ml (= 6.8 mMol l-1), advice to stop smoking to subjects who smoked more than 15 cigarettes per day. The intervention was applied for 10 years during which time CHD and stroke incidence and mortality were followed by means of special registers. Participation rate at first screening examination was 75%. The risk factor levels, i.e. blood pressure, serum cholesterol and smoking decreased markedly during 10 years in the intervention group, but also among the control groups. Total mortality, stroke and CHD incidence did not differ significantly between the intervention group and any of the two control groups. We conclude that a decrease has taken place in all three major risk factors for CHD in the general male population in Göteborg, Sweden. Strategies other than intervention on high-risk individuals must be chosen if a major impact on disease incidence is to be achieved in the general population.", "The results of a controlled trial of multiphasic screening in general practice are presented. In 1967, 7,229 individuals aged between 40 and 64 years were randomly allocated into either a Screening or Control group. The Screening group were invited to attend two screening sessions held about two years apart, while the Control group continued to receive conventional medical care. Both groups were then invited to undergo a health survey in 1972-73 which revealed no significant differences in morbidity between the two groups. Careful follow-up permitted detailed Screening-Control comparisons of various outcome measures--consultation and hospital admission rates, certified sickness absence from work, and mortality. Nine years after the initial screening, no significant differences were found between the two groups in any of the outcome measures. It is estimated that a similar screening programme for the entire middle-aged UK population would cost 142 pounds million at 1976 prices." ]
"General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although the number of new diagnoses was increased. Important harmful outcomes, such as the number of follow-up diagnostic procedures or short term psychological effects, were often not studied or reported and many trials had methodological problems. With the large number of participants and deaths included, the long follow-up periods used, and considering that cardiovascular and cancer mortality were not reduced, general health checks are unlikely to be beneficial."
"CD008613"
[ "14686958" ]
[ "Effect of hormone replacement therapy on cardiovascular risk factors in postmenopausal women with diabetes." ]
[ "Hormone replacement therapy (HRT) in postmenopausal women improves menopausal symptoms, decreases the incidence of osteoporotic fracture, but the effects on cardiovascular risk factors remain controversial.\n To test the hypothesis that HRT may have beneficial effects on the cardiovascular risk profile in postmenopausal women with diabetes.\n One hundred and fifty postmenopausal patients with type 1 (T1DM) and type 2 diabetes (T2DM) were randomized to receive HRT (Kliofem) or placebo for 12 months. We monitored the effects on cardiovascular risk factors, including lipid profile, glycaemic control, blood pressure and body weight.\n Mean low-density lipoprotein (LDL) cholesterol was associated with a nonsignificant decrease [-0.14 mmol/l (CI=-0.44, 0.17) (p=0.37)] in the Kliofem-treated group. Total cholesterol fell by 0.42 mmol/l (CI=-0.78, -0.05) (p=0.027). High-density lipoprotein (HDL) cholesterol was reduced by a mean of 0.07 mmol/l compared to a mean rise of 0.12 mmol/l on placebo. There were apparent differences in the treatment effects between T1DM and T2DM. There was no change in triglycerides or apoprotein B and no effect on glycaemic control, blood pressure or menopausal symptom scores. In the Kliofem group, BMI fell by 0.66 kg/m2 compared to an increase of 0.14 kg/m2 for placebo patients (p=0.046).\n Although the long-term effects of HRT in women with or without diabetes appear to suggest that some types of HRT either confer no cardiovascular protection or may increase risk, the impact of Kliofem diabetic women on cardiovascular risk factors is probably neutral." ]
"There is a lack of evidence around the use of HRT in women with type 1 diabetes. The one study that has been undertaken in this area is underpowered. More RCTs are required in the area to examine the impact of HRT on glycaemic control and cardiovascular outcomes."
"CD006286"
[ "17533178", "18179756", "20430451", "23119911", "7862473", "12612277" ]
[ "The role of mometasone furoate aqueous nasal spray in the treatment of adenoidal hypertrophy in the pediatric age group: preliminary results of a prospective, randomized study.", "Intranasal flunisolide treatment in children with adenoidal hypertrophy.", "Medical treatment of adenoid hypertrophy with \"fluticasone propionate nasal drops\".", "Chronic adenoid hypertrophy in children - is steroid nasal spray beneficial?", "Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction with aqueous nasal beclomethasone.", "Frequency of surgery among children who have adenotonsillar hypertrophy and improve after treatment with nasal beclomethasone." ]
[ "We evaluated the efficacy of mometasone furoate aqueous nasal spray in decreasing adenoid size and reducing the severity of chronic nasal obstruction symptoms in children affected by adenoidal hypertrophy.\n Sixty children were recruited in a 2-stage, randomized, placebo-controlled trial. All patients complained of chronic nasal obstruction symptoms, and nasal endoscopy showed >75% choanal obstruction attributable to adenoid pads. In the first stage, 30 patients (group A) underwent mometasone treatment (50 microg per nostril per day) for 40 days, and 30 children (group B) received placebo. In the second stage, at the end of the first 40-day treatment period, patients in group A who showed subjective and objective clinical improvement were divided into 2 subgroups; group A1 (11 children) received topical intranasal steroid treatment on alternate days for the first 2 weeks per month, whereas group A2 (10 children) continued daily mometasone treatment for the first 2 weeks per month. After 3 months, all children were reassessed.\n Fifty-seven children completed the study according to the protocol. After the first treatment period, the severity of symptoms and adenoid size decreased for 21 patients (77.7%) in group A. No improvement was observed in the placebo group. After 3 months of additional therapy, group A2 patients demonstrated a more-pronounced reduction in adenoid size compared with group A1 patients. No statistically significant change in symptoms was identified. Mometasone treatment was well tolerated by all patients.\n Mometasone furoate aqueous nasal spray may be considered useful in decreasing adenoid pad size and the severity of symptoms related to adenoidal hypertrophy. Children with adenoidal hypertrophy that is not associated with tonsillar hypertrophy should be considered for intranasal mometasone treatment before surgery is planned.", "Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children and it has been proposed that treatment with intranasal corticosteroids can decrease the size of AH. Therefore, the aim of the study is to evaluate the effect of the use of intranasal flunisolide among children affected by AH. 178 children with AH were evaluated in this randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to re-evaluate AH degree. Flunisolide treatment was associated with significant (p less than 0.04) reduction of AH degree. There was moreover a consistent reduction of children (46 out of 58) proposed to adenoidectomy. No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, thus preventing the recurrence to adenoidectomy, and is safe.", "Adenoid hypertrophy treatment for children is generally planned in accordance with the degree of airway obstruction and related morbidity. If surgical treatment is indicated, the individual risk/benefit analysis of patients should be assessed in terms of anesthetic and postoperative complications. Although there are few alternative treatment options, these may be considered as a nonsurgical approach in less serious cases. Accordingly, studies about intranasal steroid applications under various protocols have been presented.\n The prospective, randomized, placebo-controlled study.\n Tertiary referral center.\n Patients indicated for surgery were randomly divided into two groups. The study group was treated by fluticasone propionate nasal drops (NSD-nasal steroid drops) of 400 microg/day for 8 weeks. The control group was treated by normal saline (NS) in the same way. All the patients were called for follow-up every 4 weeks.\n At the end of 8 weeks, statistically significant improvement (p<0.05) was observed in the NSD treated group compared to the NS treated group in terms of nasal airway obstruction, mouth breathing, speech abnormalities, apnea and night cough. At the end of 8 weeks, the average total symptoms score of the NSD treated group dropped from 13.7 to 2.9 while the NS treated group's score changed from 14.8 to 14.6. After 8 weeks of NSD treatment the initial adenoid/choana (A/C) rate had dropped from 87 to 56% and a total decrease of 35.6% was observed. After 8 weeks of NS treatment the A/C rate dropped from 87 to 85% and a total decrease of 2.2% was observed.\n In this study, the effect of fluticasone propionate nasal drops on adenoid hypertrophy is examined for the first time. This method provides an effective alternative to surgical treatment in children with adenoid hypertrophy. With the protocol applied in this study 76% of the patients were eliminated the surgery and removed from the surgical waiting list.\n Copyright 2010 Elsevier Ireland Ltd. All rights reserved.", "To the efficacy of naial btvlomethosone spry in the treatmrnl of chronic adenoid hypertrophy in children.\n .-1 randomized double-blind placebo-controlled study Setting: Tertiary academic referral center Patients: Aged 3-12 years diagnosed to have chronic nasal obstruction due to hypertrophied adenoids.\n Intranasal beclomethasone at the dose of 200 microgramslday to one group and placebo to the other group in matched dispensers for 8 weeks. Outcome measures: Reduction of symptoms due to hypertrophied adenoids and the size of enlarged adenoids. Variables were noted at the beginning and end of the study for symptoms score severity. X-ray and flexible nasal endoscopie findings.\n Analysis was done to find any significant improvement between the two groups. The Chisquare test was used to investigate the relationship between discrete variables. 26 children completed the study with 13 each in the drug and placebo group. There were 17 male and 9 female patients from 3 to 12 years of age. There was no significant difference in nasal obstruction, snoring or nasal discharge between the two groups. Comparison of x-rays and endoscopy also showed no significant difference between the 2 groups significant (P value =1.000 and P=0.0666 respectively).\n This study indicates that intranasal beclomelhasone therapy is not useful in treatment of ehronic adenoid hypertrophy in the general pediatrie population.", "Pediatric adenoidal obstruction of the nasal airway is associated with significant morbidity and is a frequent indication for surgery. Because efficacious medical alternatives to adenoidectomy are lacking, we assessed the potency of standard-dose topical nasal beclomethasone in reduction of adenoidal obstruction of the nasal airway.\n Seventeen children, 5 to 11 years of age, exhibiting chronic obstructive nasal symptoms and a group mean (+/- SE) adenoid/choana ratio of 91 +/- 1% on rhinoscopic examination, completed an 8-week, double-blind, placebo-controlled crossover study of standard-dose aqueous nasal beclomethasone (total 336 micrograms/day) in the treatment of adenoidal hypertrophy. In a 16-week, open-label, follow-on study, subjects received beclomethasone 1 spray in each nostril twice daily (168 micrograms/day).\n Over the initial 4 weeks, improvements in the mean adenoidal obstruction of the choanae were significantly greater in the group receiving beclomethasone than in the group receiving placebo (right, -14.0% vs. +0.4%, P = .0002) (left, -15.0% vs. -2.0%, P = .0006). In the subsequent crossover 4 weeks, a significant beclomethasone carryover effect resulted in further adenoid size reduction in both treatment groups. All patients demonstrated a decrease in adenoid size with beclomethasone treatment, compared with a mixed response to placebo. Over the full 8-week crossover study, the mean (+/- SE) obstructive symptom score after beclomethasone treatment (20.5 +/- 3.0) was significantly improved compared to patients' initial (43.1 +/- 2.9) and placebo scores (31.1 +/- 4.2, P < or = .05), despite the active drug carryover effect into the placebo treatment period. Significant improvements in adenoidal obstruction and symptom scores over the 8-week crossover study were enhanced in the subsequent 16-week open-label period (P = .0001). By 24 weeks, an 82% reduction in group mean nasal obstruction symptom score accompanied a 29% mean reduction in adenoid/choana ratio. No clinical or demographic characteristic predicted a patient's degree of response to treatment.\n Properly administered aqueous nasal beclomethasone in standard doses can significantly reduce adenoidal hypertrophy and nasal airway obstructive symptoms in children.", "To describe the long-term outcome of a cohort of children with symptomatic adenotonsillar hypertrophy treated with aqueous nasal beclomethasone.\n The children enrolled completed a 4-week single-blind, saline solution controlled crossover study of aqueous beclomethasone (total: 400 micro g/d). In a 24-week open-label follow-on study, beclomethasone 200 micro g/d was offered to all patients. During a 100-week follow-up, the degree of nasal obstruction and the frequency of adenotonsillectomy were assessed.\n Fifty-three children of the 60 enrolled completed the study. After the 4-week crossover trial, the severity of nasal obstruction of 24 children (45%) significantly decreased during the use of nasal steroids, but no child improved when saline solution was used. At 24, 52, and 100 weeks, the 24 children who had initially improved showed a significant decrease of the severity of nasal obstruction and of the frequency of adenotonsillectomy (54% vs 83%) compared with the 29 children who had not responded after the initial steroidal therapy.\n Evidence from this study suggests that 45% of children with adenoidal hypertrophy improved after 2 weeks of steroidal therapy. Among these children, an additional 24-week treatment at a lower steroid dosage was associated with a significant 52- and 100-week clinical improvement and with reduction of adenotonsillectomy compared with children (55%) who had not responded after the initial 2-week steroidal therapy." ]
"Current evidence suggests that intranasal corticosteroids may significantly improve nasal obstruction symptoms in children with moderate to severe adenoidal hypertrophy, and this improvement may be associated with a reduction in adenoid size. The long-term efficacy of intranasal corticosteroids in these patients remains to be defined."
"CD000175"
[ "8957980", "9793807", "15321453", "719463", "10992845" ]
[ "Normal saline i.v. fluid load decreases uterine activity in active labour.", "An intravenous fluid bolus is not necessary before administration of intrathecal fentanyl for labor analgesia.", "A randomised controlled trial of fluid pre-loading before low dose epidural analgesia for labour.", "Fluid loading to reduce abnormalities of fetal heart rate and maternal hypotension during epidural analgesia in labour.", "Randomized study of intravenous fluid preload before epidural analgesia during labour." ]
[ "This study was designed to observe the effects of i.v. fluid infusion on uterine activity during normal labour in women receiving an extradural block. Thirty-four women in spontaneous labour at term gestation were allocated randomly and prospectively to one of three i.v. pre-extradural fluid load groups: group A, no fluid load; group B, normal saline 500 ml; and group C, normal saline 1000 ml. Continuous internal measurement of uterine activity was observed before, during and after fluid infusion and extradural block. In groups A and B, uterine activity did not change. In group C, uterine activity decreased after infusion of saline (P < 0.01) and returned to baseline over the next 20 min. Extradural block was not associated with a change in uterine activity. Hypotension was not increased in the group that received no fluid preload.", "To determine if an intravenous (i.v.) fluid bolus is necessary to prevent any possible hemodynamic sequelae after administration of intrathecal fentanyl in laboring parturients.\n Prospective, randomized study.\n Labor suite of a women's tertiary care hospital.\n 30 ASA physical status I and II parturients in active labor requesting labor analgesia.\n Patients were randomly divided into two groups of 15. One group received no i.v. fluid prior to the administration of 25 micrograms of intrathecal fentanyl, and the other group received 500 ml of lactated Ringer's solution before the block.\n Blood pressures [systolic (SBP), diastolic (DBP), mean (MAP)], heart rate (HR), cardiac index (CI; using impedance cardiography), and visual analog scores were measured before the block, after fluids, and then every 5 minutes for 45 minutes after the block. Prenatal baseline blood pressures before the onset of labor were obtained from the obstetrician's office records. Results were analyzed using analysis of variance. All patients reported good pain relief. No patient from either group required treatment for hypotension. In the no fluid group, SBP and MAP decreased 10% and 14%, respectively (p = 0.05), following intrathecal fentanyl administration compared with preblock values obtained duri