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[ "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." ]

[ "3174314", "3312552", "11430325", "1305392", "10228288", "3677969", "10730525", "8627434", "2231212", "21170827", "3373404", "10430197", "7035955", "7838642" ]

[ "Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants.", "Prevention of symptomatic patent ductus arteriosus with a single dose of indomethacin.", "Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.", "[Indomethacin in the prevention of subependymal-intraventricular hemorrhage in preterm newborns with conventional mechanical ventilation].", "Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants.", "Failure of prophylactic indomethacin to improve the outcome of the very low birth weight infant.", "Indomethacin prophylaxis for patent ductus arteriosus (PDA) in infants with a birth weight of less than 1250 grams.", "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.", "Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus.", "A randomized, double-masked trial of prophylactic indomethacin tocolysis versus placebo in women with premature rupture of membranes.", "Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates.", "The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.", "Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants.", "Continuous versus multiple rapid infusions of indomethacin: effects on cerebral blood flow velocity." ]

[ "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.", "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.", "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.", "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 evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants.\n Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored.\n Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar.\n A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.", "Prophylactic closure of the patent ductus arteriosus (PDA) has been recommended as a means of decreasing early respiratory distress, and thereby chronic respiratory sequelae in the very low birth weight (VLBW) neonate. This study was undertaken to evaluate some possible mechanisms for the observed failure of early indomethacin therapy to achieve such improvement. 24 VLBW infants with echocardiographic evidence of PDA were randomized to receive either indomethacin or placebo at 48 h of life; and then they were studied for clinical, metabolic and laboratory signs of ductal constriction and/or reopening. Early indomethacin conferred no improvement in respiratory sequelae. However, this was not secondary to a short-term therapeutic failure. Prophylactic indomethacin, even in the VLBW infant, was successful in decreasing dilator prostaglandin production, and probably in closing the PDA and in decreasing the number of recurrences. The implications are that even with effective ductal constriction, overall morbidity is not affected.", "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.", "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.", "We tested the hypothesis that prolonged maintenance indomethacin therapy would allow more effective closure of patent ductus arteriosus (PDA) and thereby decrease the recurrence rate. Thirty-nine low birthweight neonates (less than 1500 gm) with confirmed PDA were randomly assigned in a double-blind fashion to receive standard indomethacin therapy (three doses), followed either by maintenance indomethacin therapy (0.2 mg/kg/day) for 5 days or by an equivalent volume of placebo for 5 days. Of the 20 infants who received maintenance indomethacin therapy, two (10%) required additional therapy and one of these required surgical ligation. Of the 19 infants who received only the first three indomethacin doses, nine (47%) required additional therapy for PDA (p less than 0.05) and seven of these had a ligation (p less than 0.05). We conclude that maintenance indomethacin therapy, in comparison with short-term indomethacin therapy, decreases the incidence of surgical PDA ligations, eliminates most PDA recurrences, and does not increase toxic effects of indomethacin in the low birth weight infant with PDA.", "Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and frequently results in preterm birth, often within 48 hours of membrane rupture. Our objective was to determine if subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation benefit from a 48-hour course of prophylactic indomethacin tocolysis. This was a double-masked randomized controlled trial. Subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation were randomized to receive indomethacin or placebo for 48 hours in addition to corticosteroids and latency antibiotics. The primary outcome of the study was delivery within 48 hours. Maternal and neonatal outcomes were also compared. This study was concluded prematurely due to slow accrual after a total of 50 subjects were enrolled. A total of 23/25 (92%) subjects in the indomethacin group remained pregnant beyond 48 hours compared with 20/22 (90.9%) in the placebo group (relative risk, 1.01; 95% confidence interval, 0.84 to 1.21). The latency period medians and interquartile ranges were similar between the two groups [indomethacin 193 (92 to 376.5) hours versus placebo 199 (77.5 to 459) hours, P = 0.91], and no differences were noted in any maternal or neonatal secondary outcomes. This limited study demonstrates no benefit with the use of prophylactic indomethacin tocolysis for women with PPROM.\n © Thieme Medical Publishers.", "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.", "To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo.\n A randomised placebo-controlled trial.\n Two university teaching hospitals with level three neonatal intensive care units.\n Women in preterm labour with intact membranes between 23 and 30 weeks of gestation.\n Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion.\n The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI).\n Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group.\n There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.", "We performed a double-blind, controlled study of prophylactic indomethacin therapy in 47 premature infants (less than 1700 g) who had subclinical patent ductus arteriosus. They received either indomethacin or placebo at a mean age of 2.9 days. Among the 25 infants weighing more than 1000 g, a hemodynamically important ductus shunt developed in only four of the 14 given placebo. The incidence of important shunts, the number of surgical ligations, and the duration of oxygen therapy were not appreciably different between the study groups. In contrast, among the 22 infants who weighed 1000 g or less, a major ductus shunt developed in 10 of the 12 given placebo. In the smaller infants indomethacin therapy was associated with a significantly lower incidence of major shunts, fewer surgical ligations, a decreased duration of oxygen therapy, and fewer days necessary to regain birth weight. We conclude that prophylactic indomethacin therapy in infants weighing under 1000 g prevents the later development of large ductus shunts and decreases morbidity.", "Therapeutic administration of indomethacin for patent ductus arteriosus (PDA) closure has been documented to decrease cerebral blood flow velocity which may be harmful to the vulnerable premature neonate. We have therefore compared the effects of administering indomethacin by rapid injection versus slow, continuous indomethacin infusion at the same total therapeutic dose on middle cerebral artery (MCA) systolic and diastolic flow velocity, resistance index, and cerebral blood flow (as reflected by the integrated area under the curve).\n Premature neonates (< 1750 g) documented echocardiographically to have a PDA were randomized to receive indomethacin either by three rapid injection doses or by continuous intravenous infusion over the ensuing 36 hours, providing an equivalent total dose. Echocardiograms and transcranial color flow mapping of the MCA flow velocity were measured at baseline and serially following initiation of therapy in both groups. Effects on cerebral blood flow velocity are presented.\n Eighteen infants [rapid injection-1.2 +/- 0.3 kg (n = 9) and continuous-1.1 +/- 0.2 kg (n = 9)] were studied. In the rapid injection treated infants decreased flow velocity in the MCA as manifested by abrupt, significant decreases in systolic (to 70 +/- 8% baseline) and diastolic (to 65 +/- 13% baseline) flow velocity and area under the curve (to 60 +/- 10% of baseline) were evident by 4 minutes and progressed to 30 minutes after treatment initiation. These changes were not observed in the group treated with continuous indomethacin. Both therapeutic modalities were equally successful in closing the ductus, although the numbers are too small to definitively determine therapeutic efficacy.\n Slow, continuous infusion eliminated the decrease in cerebral flow velocity and appears to be effective in closing the PDA." ]

[ "2381003", "9848045" ]

[ "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns.", "A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds." ]

[ "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.", "A new silver-coating technology was developed to prevent wound adhesion, limit nosocomial infection, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. For the purposes of this article, Acticoat (Westaim Biomedical Inc, Fort Saskatchawan, Alberta, Canada) silver-coated dressing was used. After in vitro and in vivo studies, a randomized, prospective clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution's standard burn wound care. Thirty burn patients with symmetric wounds were randomized to be treated with either 0.5% silver nitrate solution or Acticoat silver-coated dressing. The dressing was evaluated on the basis of overall patient comfort, ease of use for the wound care provider, and level of antimicrobial effectiveness. Wound pain was rated by the patient using a visual analog scale during dressing removal, application, and 2 hours after application. Ease of use was rated by the nurse providing wound care. Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment. Patients found dressing removal less painful with Acticoat than with silver nitrate, but they found the pain to be comparable during application and 2 hours after application. According to the nurses, there was no statistically significant difference in the ease of use. The frequency of burn wound sepsis (> 10(5) organisms per gram of tissue) was less in Acticoat-treated wounds than in those treated with silver nitrate (5 vs 16). Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds (1 vs 5). Acticoat dressing offers a new form of dressing for the burn wound, but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care." ]

[ "1159434", "7355429", "15489085", "9403477" ]

[ "Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.", "Anticoagulant vs anti-platelet therapy as prophylactic against cerebral infarction in transient ischemic attacks.", "Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.", "A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group." ]

[ "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.", "156 patients with transient ischemic attacks (TIA) or reversible ischemic neurological deficit (RIND) were given prophylactic anticoagulant (AC) treatment against cerebral infarction in a prospective multicenter study from 5 hospitals in southern Sweden. After 2 months of AC treatment, 135 patients remained in the study and were randomized into 2 groups; one continued with AC treatment and one changed to anti-platelet therapy. The patients were followed for 12 months. No significant difference was seen between the 2 groups but 3 completed cerebral infarctions occurred during anti-platelet therapy against one during AC treatment. One cerebral hemorrhage was seen during AC treatment. All completed strokes occurred in men who initially had carotid symptoms. The number of patients with TIA/RIND was somewhat higher in the anti-platelet group whereas myocardial infarctions occurred more often during AC treatment. Compared to the natural history of untreated TIA/RIND both treatments were found to have a prophylactic effect against cerebral infarction.", "This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.\n Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.\n We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.\n Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.\n The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.", "Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event \"death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication.\" The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined." ]

[ "11212135", "6487909", "10780138", "8116338", "10450619", "11317951", "11777121", "8481745", "11784832", "16416356", "16816304", "20621945", "11026947" ]

[ "Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.", "An evaluation of cognitive-behaviour therapy for depression in patients with multiple sclerosis.", "Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis.", "Effects of neuropsychological treatment in patients with multiple sclerosis.", "Professional and paraprofessional group treatments for depression: a comparison of cognitive-behavioral and mutual support interventions.", "A randomized controlled trial of the effects of multi-sensory stimulation (MSS) for people with dementia.", "Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.", "A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients: I. Outcome.", "Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.", "Efficacy of a neuropsychological training programme for patients with multiple sclerosis -- a randomised controlled trial.", "Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia.", "Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial.", "Cognitive-behavioural techniques for general psychiatrists in the management of patients with psychoses." ]

[ "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.", "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.", "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 relative efficacy of professional and paraprofessional therapists in providing group cognitive-behavioral therapy (CBT) and mutual support group therapy (MSG) was examined. Depressed outpatients (N = 98) were randomly assigned to CBT or MSG led by either 2 professional or 2 paraprofessional therapists. Results suggest that nonprofessionals were as effective as professionals in reducing depressive symptoms and that clients in the CBT and MSG conditions improved equally. Clinically significant improvement was demonstrated for both conditions. However, following treatment, more patients in the professionally led CBT groups were classified as nondepressed and alleviated than in the paraprofessionally led CBT groups. Additionally, therapist adherence to manual-based treatments was associated with greater improvement in clinician-rated depressive symptoms in both conditions and skills in cognitive restructuring were associated with greater improvement among clients in CBT.", "To investigate short-term effects of Multi-Sensory Stimulation (MSS) on behaviour, mood and cognition of older adults with dementia, the generalization of effects to day hospital and home environments and the endurance of any effects over time.\n A randomized controlled trial comparing MSS with a credible control of one-to-one activities.\n Fifty patients with diagnoses of moderate to severe dementia were randomized to either MSS or Activity groups. Patients participated in eight 30-minute sessions over a 4-week period. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up assessments were taken to investigate any generalization of effects on cognition, behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased.\n Immediately after MSS and Activity sessions patients talked more spontaneously, related better to others, did more from their own initiative, were less bored/inactive, and were more happy, active or alert. Both groups were more attentive to their environment than before, with a significantly greater improvement from the MSS group. At the day hospital, patients in the Activity group improved on their 'speech skills' (amount of speech; initiation of speech), whereas the MSS group remained unchanged during the trial. The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated. No longer-term benefits were shown; indeed, behaviour declined sharply during the month follow-up period.\n Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia.", "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.", "Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive-behavioural treatments to alleviate residual hallucinations and delusions. Forty-nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow-up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect.", "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.", "One aim of this project was to investigate the efficacy of a specific training programme for MS patients which also contained compensation strategies and relaxation exercises relevant to everyday life. The other aim was to check the programme's relevance to everyday life.\n 19 patients, randomised into two groups, took part in the study. The participants in the treated group completed a specific neurological training programme which began immediately after the basic testing (visit 1) and lasted 4 weeks, with a total of 12 sessions. The monitoring test was done immediately after the training programme (at visit 2) and the follow-up was 3 months later (visit 3). Both study groups were fully comparable as regards clinical and socio-demographic data and baseline intelligence level.\n The results of the cognitive training programme were especially evident in the significant improvements in executive functions (CKV) and spatial-constructional abilities (HAWIE-R). Comparison between the treated and the control group showed no significant difference in the fatigue values (MFIS). However, when the treated group was examined over the three times of measurements, the symptoms of fatigue had diminished significantly. Regarding memory, comparison of the groups showed no changes; within the treated group; however, the verbal (VLT) and nonverbal learning and memory (NVLT) improved significantly. The results for sustained attention improved in both groups over time. It must be assumed that a learning effect had occurred here. The depression values (BDI) also improved in both study groups. The follow-up questionnaire showed that 60% (6) attributed an average to above-average benefit to the training.\n To summarise, it is apparent that MS patients with mild to moderate cognitive impairment are able to profit from even a fairly brief neuropsychological training programme and to integrate much of it into their everyday lives. In view of this, it would seem appropriate to offer such a programme as standard, associated with medication.", "Little is known about the medium-term durability of cognitive-behavioural therapy (CBT) in a community sample of people with schizophrenia.\n To investigate whether brief CBT produces clinically important outcomes in relation to recovery, symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up.\n Participants (336 of 422 randomised at baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to treatment allocation (CBT or usual care).\n At 1-year follow-up, participants who received CBT had significantly more insight (P = 0.021) and significantly fewer negative symptoms (P = 0.002). Brief therapy protected against depression with improving insight and against relapse; significantly reduced time spent in hospital for those who did relapse and delayed time to admission. It did not improve psychotic symptoms or occupational recovery, nor have a lasting effect on overall symptoms or depression at follow-up.\n Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management, family interventions and expert therapy for treatment resistance.", "We evaluated a rehabilitation programme for executive deficits in multiple sclerosis patients by comparing outcome scores of a cognitive intervention group (CIG; n = 11) with those of a placebo group (n = 14) and an untreated group (n = 15). Executive functioning and verbal learning improved significantly more in the CIG. The treatment effect on verbal learning was still present at 1-year follow-up. Baseline brain atrophy, quantified by the brain parenchymal fraction, was associated with treatment effects for one aspect of executive functioning. Consequently, cognitive intervention may be beneficial and baseline brain atrophy has some predictive value in determining treatment outcome for executive functioning.", "Recent research progress showing the benefits of cognitive therapy in schizophrenia leaves the general psychiatrist unsure whether to attempt to use such techniques.\n To test whether cognitive-behavioural techniques are beneficial in the management of patients with schizophrenia in general psychiatric practice.\n A randomised controlled study comparing the use of cognitive-behavioural techniques and befriending in schizophrenia.\n Significant improvement in symptoms occurred in the group treated with cognitive-behavioural techniques but not in the befriending group. During the 6-month follow-up period the cognitive-behavioural group tended to have shorter periods in hospital.\n General psychiatrists could help their patients with schizophrenia by using cognitive-behavioural techniques. Such techniques are well within the capability of general psychiatrists, but their application would involve more of the consultant's time spent in direct contact with patients with psychoses." ]

[ "11554954", "16492236", "9825271", "15482357", "16618262", "8427430", "15579612", "11014413" ]

[ "Efficacy of nonprescription doses of ibuprofen for treating migraine headache. a randomized controlled trial.", "Rofecoxib in the acute treatment of migraine: a randomized controlled clinical trial.", "Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks.", "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.", "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.", "Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial.", "Ibuprofen plus caffeine in the treatment of tension-type headache." ]

[ "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.", "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 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.", "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.", "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.", "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.", "The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension-type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques.\n A randomized, double-blind, parallel, multicenter, single-dose, placebo- and active-controlled study included 301 subjects diagnosed with tension-type headache. Treatment groups included ibuprofen and caffeine, ibuprofen alone, caffeine alone, or placebo. Subjects measured onset of relief (both time to first perceptible relief and time to meaningful relief) after taking a single oral dose of their assigned medication. Pain intensity and pain relief were rated over a 6-hour study period. Overall evaluation was made on completion of all other ratings.\n Ibuprofen and caffeine administered together provided significantly greater analgesic activity than ibuprofen alone, caffeine alone, and placebo. Ibuprofen and caffeine administered together demonstrated significantly shorter times to meaningful improvement in headache relief than ibuprofen or placebo; significantly greater total analgesia than ibuprofen alone, caffeine alone, or placebo; and significantly greater peak relief than ibuprofen alone, caffeine alone, or placebo. Significantly more subjects obtained meaningful headache relief with ibuprofen and caffeine administered together than with ibuprofen alone or placebo. More patients reported complete headache relief with ibuprofen and caffeine administered together than with ibuprofen alone, caffeine alone, or placebo. Ibuprofen and caffeine administered together was rated significantly better by patients than either ibuprofen alone, caffeine alone, or placebo. No subjects ended participation in the study early because of adverse events.\n Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. A double-blind study with this method suggests that ibuprofen and caffeine administered together provides greater analgesic effectiveness than either component alone." ]

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[ "Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.", "Human insulin analogue [LYS(B28), PRO(B29)]: the ideal pump insulin?", "[Comparison of intensified traditional insulin therapy and micropump therapy in pregnant women with type 1 diabetes mellitus].", "Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes.", "Evaluation of efficacy and safety of human insulin (Novo) in the treatment of insulin-dependent diabetes mellitus: a double-blind, multicenter clinical trial.", "Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients.", "Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study.", "Effects of insulin pump vs. injection treatment on quality of life and impact of disease in children with type 1 diabetes mellitus in a randomized, prospective comparison.", "Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group.", "Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.", "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 the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.", "Multiple insulin injections using a pen injector versus insulin pump treatment in young diabetic patients.", "Insulin therapy protects the central and peripheral nervous system of intensive care patients.", "Metabolic and immunologic effects of insulin lispro in gestational diabetes.", "Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus.", "Long-term effects of self-management education for patients with Type 2 diabetes taking maximal oral hypoglycaemic therapy: a randomized trial in primary care.", "Comparative double-blind trial of the effectiveness and antigenicity of semisynthetic human insulin and purified porcine insulin in newly treated diabetic subjects.", "Human (semisynthetic) insulin and porcine insulin in the treatment of non-insulin-dependent diabetes. A double-blind, comparative clinical trial.", "[Effectiveness of treatment with metformin in patients with type 2 diabetes mellitus poorly controlled with insulin treatment].", "Continuous subcutaneous glucose monitoring improved metabolic control in pediatric patients with type 1 diabetes: a controlled crossover study.", "A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control.", "Comparison of the safety and effectiveness of human and bovine long-acting insulins.", "Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: the RealTrend study.", "Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight.", "Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women.", "Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of subjects with type 2 diabetes.", "Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure.", "Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes.", "A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine.", "A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes.", "A strategy for selection of elderly type 2 diabetic patients for insulin therapy, and a comparison of two insulin preparations.", "A twelve month double-blind randomized study of the efficacy and immunogenicity of human and porcine insulins in non-insulin-dependent diabetics.", "Continuous glucose monitoring-guided insulin adjustment in children and adolescents on near-physiological insulin regimens: a randomized controlled trial.", "Low doses of insulin as a treatment of tardive dyskinesia: conjuncture or conjecture?", "A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance.", "[Long-term effect of combination glibenclamide-insulin treatment in the secondary failure of sulfonylurea therapy--results of a one-year double blind study].", "Long-term improvement in insulin sensitivity by changing lifestyles of people with impaired glucose tolerance: 4-year results from the Finnish Diabetes Prevention Study.", "Insulin adjustment by a diabetes nurse educator improves glucose control in insulin-requiring diabetic patients: a randomized trial.", "Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.", "Early insulin therapy in very-low-birth-weight infants.", "Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes.", "Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.", "Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors.", "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.", "A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes." ]

[ "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 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.", "Ten pregnant women, affected by type I diabetes mellitus, observed for the first time during the II-III month of pregnancy, were examined. These patients were divided in two groups at random: group A underwent continuous subcutaneous insulin infusion with micropump CPI 9100 Lilly; group B underwent intensified insulin therapy with three daily doses of MC rapid insulin, two of which associated with MC intermediate insulin. All the patients were able to monitor their own blood glucose levels at home by means of reactive strips and reflectometer. In both the groups the mean glycemic values during fast and two hours after meals, and the eventual presence of urinary keton bodies and hypoglycemic crisis were evaluated during the course of pregnancy: these parameters turned out to be identical in the two groups. The increased need of insulin, the maternal body weight gain, the week and mode of delivery, the neonatal weight and the maternal and fetal complications also turned out to be identical in the two groups. To conclude, a good maternal metabolic control can be obtained either with the intensified conventional insulin therapy of with micropumps, if the patients, being properly instructed, are responsible for the monitoring of their own blood glucose levels at home.", "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 safety and efficacy of human insulin (Novo) were evaluated in a double-blind, parallel, multicenter trial in which 47 insulin-dependent diabetic patients were randomly divided into two equal groups and treated with either purified pork or human insulin (Actrapid and Monotard, Novo) for 12 wk. Mean levels of fasting plasma glucose, glycohemoglobin, and daily insulin dosages showed no statistical differences between the two groups, and there was no significant difference in the incidence of hypoglycemic reactions. The results from this clinical trial indicate that human insulin, prepared by enzymatic transpeptidation of pork insulin, appears to be as safe and efficacious as purified pork insulin in the treatment of insulin-dependent diabetes mellitus.", "Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs).\n Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization.\n Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group.\n In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.", "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.", "Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control.\n An open, parallel, randomized controlled prospective comparative study lasting 14 months was completed by 38 type 1 children with diabetes (age 4-16 yr) following a 3.5-months run-in phase. Standardized quality-of-life Pediatric Quality of life Inventory (PedsQL) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters. Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality.\n Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment. Treatment group comparisons did not show significant improvement. Pump treatment resulted in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22% after run in.\n Within-patient comparison suggests that metabolic control, frequency of severe hypoglycaemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections.", "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.", "Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.", "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.", "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.", "Continuous subcutaneous insulin infusion (CSII) of 6 months duration was compared with 6 months of multiple insulin injections (MII) using a pen injector (NovoPen) in a prospective cross-over study with 20 young insulin dependent diabetics by evaluating metabolic control, insulin requirements and patient acceptability. Following both intensified regimens (CSII/MII) serum fructosamine declined significantly from 4.1 +/- 0.7 to 3.4 +/- 0.5 mmol/l and 3.6 +/- 0.7 mmol/l respectively (normal range: 2.2 +/- 0.2 mmol/l). When comparing CSII and MII no significant differences could be demonstrated in mean blood glucose (MBG), fasting plasma ketone bodies, fasting plasma free fatty acids (FFA), fasting plasma human growth hormone (HGH), fasting plasma glucagon or serum fructosamine. Mean insulin requirement was 11.4% higher during MII and glucose instability--demonstrated by the M-values and by the frequency of blood glucose values below 4 mmol/l--was significantly (p less than 0.02) higher during the MII treatment. All of the patients reported a better well-being on both treatment regimens and none of them wanted to go back to conventional therapy (CT). In conclusion, on a long-term basis both regimens result in identical metabolic control, but due to physical discomfort during pump treatment, the insulin pen injector was preferred by the majority (80%) of the patients.", "To investigate the effectiveness of maintaining blood glucose levels below 6.1 mmol/L with insulin as prevention of secondary injury to the central and peripheral nervous systems of intensive care patients.\n The authors studied the effect of intensive insulin therapy on critical illness polyneuropathy (CIPNP), assessed by weekly EMG screening, and its impact on mechanical ventilation dependency, as a prospectively planned subanalysis of a large randomized, controlled trial of 1,548 intensive care patients. In the 63 patients admitted with isolated brain injury, the authors studied the impact of insulin therapy on intracranial pressure, diabetes insipidus, seizures, and long-term rehabilitation at 6 and 12 months follow-up.\n Intensive insulin therapy reduced ventilation dependency (p = 0.0007; Mantel-Cox log rank test) and the risk of CIPNP (p < 0.0001). The risk of CIPNP among the 405 long-stay (> or =7 days in intensive care unit) patients was lowered by 49% (p < 0.0001). Of all metabolic and clinical effects of insulin therapy, and corrected for known risk factors, the level of glycemic control independently explained this benefit (OR for CIPNP 1.26 [1.09 to 1.46] per mmol blood glucose, p = 0.002). In turn, prevention of CIPNP explained the ability of intensive insulin therapy to reduce the risk of prolonged mechanical ventilation (OR 3.75 [1.49 to 9.39], p = 0.005). In isolated brain injury patients, intensive insulin therapy reduced mean (p = 0.003) and maximal (p < 0.0001) intracranial pressure while identical cerebral perfusion pressures were obtained with eightfold less vasopressors (p = 0.01). Seizures (p < 0.0001) and diabetes insipidus (p = 0.06) occurred less frequently. At 12 months follow-up, more brain-injured survivors in the intensive insulin group were able to care for most of their own needs (p = 0.05).\n Preventing even moderate hyperglycemia with insulin during intensive care protected the central and peripheral nervous systems, with clinical consequences such as shortening of intensive care dependency and possibly better long-term rehabilitation.", "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.", "The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).\n Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire.\n There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p <or= 0.01 at all screening visits). There were no episodes of ketoacidosis and there was no significant difference regarding severe hypoglycemia between the treatment groups.\n CSII treatment proved to be a safe therapy in children/adolescents followed for 24 months after onset of their diabetes. Treatment satisfaction was higher in the CSII group, although there was no difference in metabolic control compared with the MDI group.", "Education is an essential part of the management of patients with Type 2 diabetes, but the long-term effects are unclear and not well investigated in primary care.\n Fifty-four patients (39-75 years) treated with maximal dosages of oral hypoglycaemic agents, needing to start insulin (HbA(1c)> or = 7.0%), were randomly allocated to a 6-month educational programme by a diabetes nurse (DN group) or usual care (UC group). Main outcome measures were HbA(1c), number of patients with HbA(1c) < 7.0%, and number of patients treated with insulin 18 months after baseline.\n Six weeks after the intervention HbA(1c) levels had improved from 8.2 (1.1) to 7.2 (1.3) in the DN group, and from 8.8 (1.5) to 8.4 (1.7) in the UC group. Adjusted for baseline values, at 6 weeks HbA(1c) improved 0.7% (95% confidence interval 0.1, 1.4) more in DN than in UC. Of the patients in DN, 60% reached HbA(1c) < 7.0% compared with 17% in UC (P < 0.01). However, at 18 months there were no significant differences for HbA(1c), number of patients with HbA(1c) < 7.0%, or number treated with insulin.\n Education was effective in improving glycaemic control and in delaying the need for insulin therapy in patients treated with maximal oral hypoglycaemic therapy. The reduced effect after 1 year was probably due to the discontinuation of the educational programme. Short-term education should not be offered without regular reinforcements integrated into standard diabetes care.", "A double-blind comparative trial of the effectiveness and antigenicity of semisynthetic human insulin (Novo) and highly purified (Monocomponent) porcine insulin was performed over a 12 month period in 20 diabetic subjects newly treated with insulin. Human insulin was shown to be indistinguishable from porcine insulin of comparable purity with respect to plasma glucose and glycosylated hemoglobin levels and insulin dose requirements. Human insulin was no less antigenic than porcine insulin; significant IgG-associated insulin binding activity was detected in six of the ten patients in the human insulin treated group and four of the ten patients in the porcine insulin treated group. In all patients, the binding activity was of low capacity. No adverse reactions to human insulin were noted. It is concluded that semisynthetic human insulin, like purified porcine insulin, is safe and effective. Although there may be advantages for human insulin in the setting of insulin allergy, this study does not indicate that human insulin has advantages over purified porcine insulin with respect to elicitation of antibodies of the IgG class.", "Twenty-one patients with non-insulin-dependent diabetes, who had not previously received insulin therapy, participated in a double-blind comparative trial of six months' duration to evaluate the efficacy of human (semisynthetic) insulin. Patients were allocated at random to treatment either with human (semisynthetic) insulin (10 patients) or with an equivalent porcine insulin regimen (11 patients). Sex ratio, age, body mass index, duration of diabetes, C-peptide concentrations, baseline metabolic control and initial insulin requirements were similar in both groups. After six months, no significant differences between the treatment effects of human (semisynthetic) insulin and porcine insulin, as assessed by measurements of fasting and postprandial plasma glucose levels, the concentration of glycosylated haemoglobin, serum lipid levels, insulin dose, and body weight, were found. No adverse reactions, injection-site anomalies, or drug-related biochemical abnormalities were noted in either group. It was concluded that human (semisynthetic) insulin is as effective as porcine insulin in initiating the treatment of patients with non-insulin-dependent diabetes who require insulin therapy.", "Combined treatment with insulin plus metformin could be a good alternative to improve the glycemic control in patients with type 2 diabetes mellitus poorly controlled with insulin therapy. We retrospectively studied 21 obese insulin-treated type 2 diabetic patients with deficient metabolic control (HbA1c 9.2 +/- 1.2%) who were treated with metformin for a minimum of 8 months. After 4 months of treatment, a significant decrease in the percentage of HbA1c was observed (delta HbA1c -1.07 +/- 1.12%; p < 0.01), with maintained values since then. Non changes in body weight or insulin requirement were noted. Our results suggest that the addition of metformin to insulin treatment is a safe and effective strategy for the improvement of glycemic control among obese type 2 diabetic patients.", "To improve metabolic control and prevent complications, both acute and late, we need to adjust treatment on the basis of the blood glucose (BG) profile, as not even the most active BG self-monitoring gives sufficient information.\n We have used Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA) in a controlled crossover study including 27 diabetic patients aged 12.5 +/- 3.3 (mean; standard deviation; range: 5-19) years. All patients were treated with intensive insulin therapy, 14 with multiple injections, and 13 with pumps. The patients were randomized into an open or blind study arm. Both arms wore the CGMS sensor for 3 days every 2 weeks. CGMS profiles were used in the open study arm to adjust insulin therapy at follow-up visits every 6 weeks. Both the patients and the diabetes team were masked to the CGMS profiles in the blinded arm, and insulin therapy adjustments were based solely on 7-point BG profiles performed by the patients. At 3 months the 2 study arms were crossed over.\n Despite initial problems with a device new to both patients and the diabetes team, hemoglobin A(1)C decreased significantly in the open arm (from 7.70%-7.31%) but not in the blind arm (7.75%-7.65%). A total of 26/27 patients experienced daytime low subcutaneous glucose (<3.0 mmol/L;.8 episodes/day; duration 58 +/- 29 minutes; 5.5% of total time), and 27/27 patients had at least 1 nocturnal episode of low subcutaneous glucose (.4 episodes/night; duration 132 +/- 81 minutes; 10.1% of total time).\n Use of CGMS facilitated an improved treatment, and patients received new insight and increased motivation. In this study, we found CGMS to be a useful tool for education and improving metabolic control.", "To assess in a randomized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-standing poor glycemic control.\n A total of 79 patients in 11 Dutch centers were randomized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order. Glycemic control was assessed by HbA(1c), self-reported hypoglycemic events, and blood glucose memory meter read outs. Changes in quality of life were assessed by self-report questionnaires administered at baseline and 16 weeks.\n As the drop-out rate after crossover was high (17 of 79 patients [22%]), we analyzed the trial as a parallel clinical trial, using data of the first half of the crossover phase only. At 16 weeks, mean HbA(1c) was 0.84% (95% CI -1.31 to -0.36) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group (P = 0.002). Stability of blood glucose self-measurement values, expressed as SD of the nine-point blood glucose profiles, improved in the insulin pump group by 29.3 +/- 41.1 vs. 8.2 +/- 36.5% in the injection group (P = 0.039). The number of mild hypoglycemic episodes per patient-week was 0.99 (95% CI 0.11-1.87) higher in the insulin pump group (P = 0.028). Weight gain was similar in both groups. Scores on the Short-Form 36-Item subscales 'general health' and 'mental health' improved in the continuous subcutaneous insulin infusion group, compared with stable values in the injection group (P = 0.048 and 0.050, respectively).\n Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control.", "Since ultralente insulin pharmacokinetics suggest faster absorption by human insulin when compared with bovine insulin using the subcutaneous route, the safety and efficacy of human ultralente in the outpatient setting was evaluated. Twenty type I patients participated in a randomized study using a crossover design of four six-week phases: (a) one daily injection of human ultralente; (b) two daily injections of human ultralente; (c) one daily injection of bovine ultralente and (d) two daily injections of bovine ultralente. Pre-meal human regular insulin was used with ultralente insulins and comprised 39 +/- 2% of the total daily insulin dose. Total and ultralente daily insulin doses were lower with human ultralente insulin (51.3 +/- 3.0 total and 30.9 +/- 3.4 ultra lente u/day) when compared to bovine ultralente insulin (57.8 +/- 4.4 and 36.1 +/- 4.4 u/day, p less than 0.01), yet the metabolic control achieved was virtually identical during both phases: (hemoglobin Alc 8.6 +/- 0.2% human vs. 8.4 +/- 0.4 bovine, p = NS). The frequency of mild hypoglycemia was 3.0 +/- 0.5 events per week vs 2.0 +/- 0.3 (p = NS). No severe hypoglycemia occurred. There were no differences between blood glucose daily profiles, insulin doses, hemoglobin Alc (8.6 +/- 0.4% BID vs. 8.4 +/- 0.3% QD injections) and occurrence of hypoglycemia between the single and two-dose long-acting regimens. These data indicate that long-acting semi-synthetic human insulin (a) can be effectively used as a once daily injection, (b) may be more biologically active than bovine, and (c) can be associated with safe and effective diabetes control.", "To compare the improvements in glycemic control associated with transitioning to insulin pump therapy in patients using continuous glucose monitoring versus standard blood glucose self-monitoring.\n The RealTrend study was a 6-month, randomized, parallel-group, two-arm, open-label study of 132 adults and children with uncontrolled type 1 diabetes (A1C >or=8%) being treated with multiple daily injections. One group was fitted with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated continuous subcutaneous glucose monitoring (CGM) capability, with instructions to wear CGM sensors at least 70% of the time. Conventional insulin pump therapy was initiated in the other group (continuous subcutaneous insulin infusion [CSII] group). Outcome measures included A1C and glycemic variability.\n A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group -0.81 +/- 1.09%, P < 0.001; CSII group -0.57 +/- 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear >or=70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group -0.96 +/- 0.93%, P < 0.001; CSII group -0.55 +/- 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia.\n CGM-enabled insulin pump therapy improves glycemia more than conventional pump therapy during the first 6 months of pump use in patients who wear CGM sensors at least 70% of the time.", "Macrosomia occurs in infants of diabetic mothers in spite of \"nearly normal maternal blood glucose levels\" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin.\n Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge.\n Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01).\n Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.", "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.", "In a previous study, we found observational evidence of improvement in beta-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study.\n A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.\n Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS) and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x 10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group.\n Rosiglitazone, but not insulin, induced a recovery of pancreatic beta-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.", "Comparison of the effectiveness of combined therapy vs. an insulin regimen in NIDDM patients with secondary failure of oral hypoglycemic agents. RESEARCH DESIGN, PATIENTS AND METHODS: 27 NIDDM patients were randomly allocated to Group A (n = 14, insulin) and Group B (n = 13, insulin and sulfonylurea) with crossover after 3 months. After the next 3 months a decision was made about the further treatment according to the metabolic control. The patients were then treated for another year with the more successful regimen. Metabolic control, residual beta-cell secretory capacity, degree of peripheral insulin resistance (clamp) and insulin dose were followed during the whole study.\n (median, interquartile range, in brackets; *, statistically significant difference at P < 0.05): the combined therapy was better than insulin alone in 2/3 of patients. Glycemic control was better (HbA1c at 3 months: Group A = 7.9(1.1)% vs. Group B = 7.0(0.5)%*; HbA1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%. Insulin dose was lower during the combined therapy in the first 3 months: Group A = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight*. Combined treatment was associated with increased C-peptide excretion both fasting and postprandially. No significant differences in peripheral insulin resistance were noted between the two groups. The combined treatment remained successful even after one year. The two groups of patients with different effective treatment did not differ significantly in any of the observed parameters.\n the combined therapy was more effective than insulin alone. Its favourable effect persisted after treatment for a year. It seems better to start the treatment of the oral failure with combined therapy compared with insulin first and later followed by combined therapy. On the basis of the observed parameters it is impossible to determine in advance which kind of treatment is more suitable for the individual patient.", "The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin.\n In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively.\n Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001).\n Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.", "The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c) levels in children and adolescents with type 1 diabetes.\n Thirty-two youth with type 1 diabetes (age 8-21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c). HbA(1c), total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy.\n While there was no significant change in the glargine group (HbA(1c) 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA(1c) levels, from 8.1 to 7.2% after 16 weeks of therapy (P < 0.02 vs. baseline and <0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P < 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P < 0.01).\n Lower HbA(1c) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes.", "This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs.\n This was a multinational, 52-week, openlabel, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who had been receiving an OAD or insulin, with or without OADs, for > 4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and a-glucosidase inhibitors were discontinued at study entry, and existing OADs were continued. Doses of detemir and glargine were titrated to achieve a prebreakfast (and predinner for detemir administered twice daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs).\n The intention-to-treat population included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5% were receiving > or = 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily. There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses of basal and prandial insulins at the end of the study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs).\n when used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs.", "Sixty-six patients with secondary failure to oral hypoglycaemic therapy were assessed in hospital, and those whose fasting blood glucose concentration was greater than or equal to 10.0 mmol l-1 were treated with insulin once a day for 6 months. Only 22 patients fulfilled this criterion, and they were randomly allocated to a daily injection of either Humulin-Zn (12 patients) or Neulente insulin (10 patients). The remaining patients were considered to be noncompliant with therapy. At the end of 6 months' insulin therapy a significant (p less than 0.05) improvement occurred in HbA1c from a median (range) of 13.2(9.8-16.4)% and 13.1(10.5-16.2)% to 10.6(8-14.2)% and 11.2(8.7-13.5)% in patients given Humulin-Zn and Neulente, respectively. However, there were 46 episodes of hypoglycaemia reported by patients who received Humulin-Zn, 36 of which occurred between 0300 and 0600 h. Only four episodes were reported by the Neulente-treated group. In addition, six patients treated with Humulin-Zn (but only one patient on Neulente insulin) required the addition of short-acting insulin. The patients not treated with insulin showed a significant (p less than 0.05) improvement in blood glucose control 2 months after in-patient assessment but this improvement was not sustained to 6 months.", "This study aims to compare the effectiveness and immunogenicity of semisynthetic human insulin (NOVO) and highly purified (monocomponent) porcine insulin over a 12 month period in 16 non-insulin-dependent diabetic subjects not previously exposed to insulin. Sixteen patients were randomly allocated for treatment with either human (n = 9) or monocomponent porcine (n = 7) insulin in a double-blind trial. Both groups were identical with respect to age, sex and measures of metabolic control. Significant insulin antibody was detected in seven of the nine patients (78%) 3 months after the commencement of human insulin therapy whereas it was detected in all patients (100%) in the group treated with monocomponent porcine insulin as early as 2 months after insulin therapy. Besides the delayed rise of insulin antibodies during the first 3 months of human insulin therapy, it tended to have a lower mean insulin antibody titer, though statistically insignificant, at the end of the study. No adverse reaction to either type of insulins was noted. It is concluded that both semisynthetic human and monocomponent porcine insulin were safe and effective. Although human insulin showed a slightly lower immunogenicity than monocomponent porcine insulin of the same formulation and purities, it was not non-immunogenic. Hence, there is no reason to treat all insulin-requiring diabetic subjects with human insulin except those who have developed insulin allergy or those at risk or with a history of allergy.", "This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine.\n Pediatric subjects were recruited if they had an HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group.\n There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (-0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia.\n CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting.", "Tardive dyskinesia (TD) induced by antipsychotic drugs represents a great concern for patients and psychiatrists. Considering its pathophysiological mechanisms, there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD. Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent. In the brain, under normal conditions, energy is almost exclusively provided by glucose utilization. We thus hypothesized that, if glucose availability were reduced, the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability. Twenty chronic schizophrenic outpatients (13 males, 7 females), aged 20-67 (mean: 38.3), accepted to participate in this double-blind, placebo-controlled study. They were randomly assigned to either the insulin treatment group (10 patients) or to the insulin-placebo group (10 patients). They received a subcutaneous injection of 10 units of standard insulin or placebo at 10 a.m. From day 1 to day 15, injections were performed daily and, thereafter, every other week for 5 weeks totalizing 20 injections in 90 days. At day 7, the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study. By contrast, no change in TD symptomatology was observed in the insulin-placebo-treated group. Although a direct effect on DA neurones, or at least the participation of such an effect, cannot be excluded, our data favor a role of decreased glucose availability in reversing receptor hypersensitivity.", "To determine whether a continuous insulin infusion improves glucose tolerance in extremely low birth weight infants, we conducted a prospective, randomized trial in 24 neonates 4 to 14 days old (mean birth weight 772.9 +/- 128 gm; mean gestational age 26.3 +/- 1.6 weeks). Infants who had glucose intolerance were randomly assigned to receive either intravenous glucose and total parenteral nutrition with insulin through a microliter-sensitive pump or standard intravenous therapy alone. One infant assigned to receive insulin never required it. The groups were similar in birth weight, gestational age, race, gender, medical condition, and energy intake before the study. The mean duration of therapy was 14.6 days (range 7 to 21 days). During the study, the 11 insulin-treated infants tolerated higher glucose infusion rates (20.1 +/- 2.5 vs 13.2 +/- 3.2 mg/kg/min (1.1 +/- 0.1 vs 0.7 +/- 0.2 mmol/L); p less than 0.01), had greater nonprotein energy intake (124.7 +/- 18 vs 86.0 +/- 6 kcal/kg/day; p less than 0.01), and had better weight gain (20.1 +/- 12.1 vs 7.8 +/- 5.1 gm/kg/day; p less than 0.01) than the 12 control infants. The incidence of hypoglycemia, electrolyte imbalance, chronic lung disease, and death did not differ between groups. We conclude that a controlled insulin infusion improves and sustains glucose tolerance, facilitates provision of calories, and enhances weight gain in glucose-intolerant premature infants.", "The long-term efficacy of combined insulin-glibenclamide treatment was investigated in 79 secondary drug failure patients by means of a double-blind, randomized placebo-controlled study. During a one-year follow-up period the patients on insulin plus glibenclamide required significantly lower exogenous insulin doses. Coincidentally, C-peptide concentrations were significantly raised in the verum versus the placebo group. Additionally, the administration of glibenclamide resulted in a decreased level of hyperglycaemia during the first six months of the observation period. Glibenclamide withdrawal after six and again after twelve months of the combined therapy provoked a deterioration of glycaemic control, as well as a lowering of the C-peptide concentrations. The findings demonstrate a prolonged beneficial effect of the combined treatment, in contrast to the solely short-term effects predicted by numerous studies. The metabolic improvement must be ascribed in part to the beta-cytotropic effect of glibenclamide. Extrapancreatic pathways via receptor/postreceptor mechanisms cannot be excluded.", "Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance (IGT). However, it is unknown whether this is due to improved insulin sensitivity or insulin secretion. We investigated at baseline insulin sensitivity and insulin secretion applying frequently sampled intravenous glucose tolerance test (FSIGT) in 87 of 101 obese middle-aged subjects with IGT randomized into an intervention or a control group in the Finnish Diabetes Prevention Study. FSIGT was repeated after 4 years in 52 people. There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups. The 4-year weight and waist circumference decreases were greater in the intervention than in the control group (P = 0.043 and P = 0.025, respectively). At 4-year examination, insulin sensitivity (Si) tended to be higher in the intervention group (the difference between the mean values 36%; P = 0.067, and P = 0.136 after adjustment for age, sex, BMI, and baseline Si value). There was strong correlation between the 4-year changes in Si and weight (r = -0.628 and r = -0.710, for intervention and control groups; P < 0.001 for both). In the entire group, Si improved by 64% in the highest tertile of weight loss but deteriorated by 24% in those who gained weight (lowest tertile). Acute insulin response declined significantly in the control group. In conclusion, Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT. Insulin secretion remained constant for years in individuals with IGT who were able to lose weight.", "Diabetic patients taking insulin often have suboptimal glucose control, and standard methods of health care delivery are ineffective in improving such control. This study was undertaken to determine if insulin adjustment according to advice provided by telephone by a diabetes nurse educator could lead to better glucose control, as indicated by level of glycated hemoglobin (HbA1c).\n The authors conducted a prospective randomized trial involving 46 insulin-requiring diabetic patients who had poor glucose control (HbA1c of 0.085 or more). Eligible patients were those already taking insulin and receiving endocrinologist-directed care through a diabetes centre and whose most recent HbA1c level was 0.085 or higher. The patients were randomly assigned to receive standard care or to have regular telephone contact with a diabetes nurse educator for advice about adjustment of insulin therapy.\n At baseline there was no statistically significant difference between the 2 groups in terms of HbA1c level (mean [and standard deviation] for standard-care group 0.094 [0.008] and for intervention group 0.096 [0.010]), age, sex, type or duration of diabetes, duration of insulin therapy or complications. After 6 months, the mean HbA1c level in the standard-care group was 0.089 (0.010), which was not significantly different from the mean level at baseline. However, the mean HbA1c level in the intervention group had fallen to 0.078 (0.008), which was significantly lower than both the level at baseline for that group (p < 0.001) and the level for the standard-care group at 6 months (p < 0.01).\n Insulin adjustment according to advice from a diabetes nurse educator is an effective method of improving glucose control in insulin-requiring diabetic patients.", "To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone.\n Randomized controlled double-blind trial.\n A referral center in Caracas, Venezuela.\n One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention.\n One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo.\n Frequencies of ovulation and serum free T after 6 months.\n Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone.\n These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.", "Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.\n In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.\n As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).\n Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)\n 2008 Massachusetts Medical Society", "Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors.\n In this 1-year, multicenter, randomized, controlled trial, we compared the efficacy of sensor-augmented pump therapy (pump therapy) with that of a regimen of multiple daily insulin injections (injection therapy) in 485 patients (329 adults and 156 children) with inadequately controlled type 1 diabetes. Patients received recombinant insulin analogues and were supervised by expert clinical teams. The primary end point was the change from the baseline glycated hemoglobin level.\n At 1 year, the baseline mean glycated hemoglobin level (8.3% in the two study groups) had decreased to 7.5% in the pump-therapy group, as compared with 8.1% in the injection-therapy group (P<0.001). The proportion of patients who reached the glycated hemoglobin target (<7%) was greater in the pump-therapy group than in the injection-therapy group. The rate of severe hypoglycemia in the pump-therapy group (13.31 cases per 100 person-years) did not differ significantly from that in the injection-therapy group (13.48 per 100 person-years, P=0.58). There was no significant weight gain in either group.\n In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (Funded by Medtronic and others; ClinicalTrials.gov number, NCT00417989.)\n 2010 Massachusetts Medical Society", "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.", "The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These positive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile < 10 mmol.l-1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile > 10 mmol.l-1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day). Metformin was well tolerated by all diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.\n Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.\n At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C </= 7.0%; [corrected] there was a trend towards [corrected] the proportion achieving this without hypoglycemia being [corrected] higher with insulin detemir than with NPH insulin (34% [corrected] vs. 25[corrected]%, P = 0.052[corrected]). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was -1.58 (P < 0.001).\n Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain." ]

[ "15671460", "16322168" ]

[ "The State Children's Health Insurance Program: a multicenter trial of outreach through the emergency department.", "A randomized, controlled trial of the effectiveness of community-based case management in insuring uninsured Latino children." ]

[ "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.", "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." ]

[ "683224", "8477163", "3794867", "671204", "3312553" ]

[ "Low positioning of umbilical-artery catheters increases associated complications in newborn infants.", "Randomized trial of umbilical arterial catheter position: clinical outcome.", "Efficacy of thromboresistant umbilical artery catheters in reducing aortic thrombosis and related complications.", "Umbilical artery catheters: high, low, or no.", "Effect of heparin infusates in umbilical arterial catheters on frequency of thrombotic complications." ]

[ "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.", "Previous in vitro and in vivo reports suggest that catheters constructed of polyurethane with heparin bonded to the surface (HB-PU) are less thrombogenic than catheters made of polyvinyl chloride (PVC). A randomized trial sufficiently large (power 80%) to detect a reduction in the incidence of umbilical artery (UA) catheter complications, including aortic thrombus formation, from 45% to 20% was conducted in 125 infants. The infants were monitored for complications possibly related to the use of a UA catheter, such as systemic hypertension and abnormalities of lower extremity perfusion. The presence of aortic thrombi was assessed by ultrasound study 3.5 +/- 1.2 (SD) days and 11.1 +/- 2.3 days after insertion of the catheter. The use of HB-PU umbilical catheters did not lead to a significant reduction in the incidence of complications and aortic thrombi compared with the use of PVC catheters. The lack of reduction may have been related to the prolonged duration of catheter use in both groups. A much larger study would have been required to detect a smaller, but perhaps clinically significant, reduction in catheter-associated complications.", "nan", "We studied 111 infants requiring an umbilical artery catheter, 59 with heparin and 52 without. Thirty-four thrombi were detected, 16 in the heparin group and 18 in the control group. The numbers of thrombi in the two groups was not significantly different, but the number of clotted or nonfunctioning umbilical artery catheters was greater in the control group (P less than 0.05), as was the incidence of hypertension (P less than 0.05). There were no other significant differences between the two groups. We conclude that the use of low doses of heparin may not change the incidence of umbilical artery catheter-related thrombi, but it does appear to lower the incidence of their sequelae." ]

[ "21955873", "7740012", "19025276", "19822836", "14993087", "7673531", "14636795", "2246637", "11291373", "11850136", "18468543", "3634129", "9644411", "10168574", "15801580", "11550729", "19443788", "7805822", "4003636", "17173716" ]

[ "Web-based intervention for adolescent nonsmokers to help parents stop smoking: a pilot feasibility study.", "The television, school, and family smoking prevention and cessation project. VIII. Student outcomes and mediating variables.", "Using the internet to assist smoking prevention and cessation in schools: a randomized, controlled trial.", "Group-randomized trial of a proactive, personalized telephone counseling intervention for adolescent smoking cessation.", "Effects of an advocacy intervention to reduce smoking among teenagers.", "Preventing escalation in problem behaviors with high-risk young adolescents: immediate and 1-year outcomes.", "A randomized trial of a family-based smoking prevention intervention in managed care.", "The impact of physicians' brief smoking cessation counseling: a MIRNET study.", "The influence of a family program on adolescent tobacco and alcohol use.", "A randomized controlled trial of two primary school intervention strategies to prevent early onset tobacco smoking.", "An informal school-based peer-led intervention for smoking prevention in adolescence (ASSIST): a cluster randomised trial.", "Reducing adolescent smoking: a comparison of peer-led, teacher-led, and expert interventions.", "A preliminary study of the use of peer support in smoking cessation programs for pregnant adolescents.", "Provocative appeals in anti-smoking mass media campaigns targeting adolescents--the accumulated effect of multiple exposures.", "Behavioral counseling for reducing children's ETS exposure: implementation in community clinics.", "Randomized trial of brief family interventions for general populations: adolescent substance use outcomes 4 years following baseline.", "Contingency management and motivational enhancement: a randomized clinical trial for college student smokers.", "[Results of a controlled randomized study on prevention of smoking habit in adolescents].", "Skills intervention to prevent cigarette smoking among adolescents.", "Efficacy of an emergency department-based motivational teenage smoking intervention." ]

[ "A novel approach to tobacco control is to engage adolescent nonsmokers in support roles to encourage and help their parents stop smoking. This pilot study examined the feasibility and potential efficacy of a web-based support skills training (SST) intervention for adolescents to help a parent stop smoking. Forty nonsmoking adolescents 13-19 years of age (70% female, 93% White) were enrolled and randomly assigned to a health education (HE) control group (n=20) or SST (n=20). Both consisted of written materials and five weekly, 30 min, web-based, counselor-facilitated group sessions. Parents were enrolled for assessments only. Adolescents and parents completed assessments at baseline, week 6 (post-treatment), week 12 and 6-months follow-up. Both interventions were feasible based on treatment acceptability ratings, study retention and treatment compliance. The biochemically confirmed 6-month smoking abstinence rate was higher for parents linked to teens in HE (35%, 7/20) than in SST (10%, 2/20), p=0.13. About half of parents in each group reported a quit attempt since study enrollment. Teens can be engaged to help parents stop smoking. Future research is warranted on determining effective intervention approaches.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "This paper presents the student outcomes of a large-scale, social-influences-based, school and media-based tobacco use prevention and cessation project in Southern California.\n The study provided an experimental comparison of classroom delivery with television delivery and the combination of the two in a 2 x 2 plus 1 design. Schools were randomly assigned to conditions. Control groups included \"treatment as usual\" and an \"attention control\" with the same outcome expectancies as the treatment conditions. Students were surveyed twice in grade 7 and once in each of grades 8 and 9. The interventions occurred during grade 7.\n We observed significant effects on mediating variables such as knowledge and prevalence estimates, and coping effort. The knowledge and prevalence estimates effects decayed partially but remained significant up to a 2-year follow-up. The coping effort effect did not persist at follow-ups. There were significant main effects of both classroom training and TV programming on knowledge and prevalence estimates and significant interactions of classroom and TV programming on knowledge (negative), disapproval of parental smoking, and coping effort. There were no consistent program effects on refusal/self-efficacy, smoking intentions, or behavior.\n Previous reports demonstrated successful development and pilot testing of program components and measures and high acceptance of the program by students and parents. The lack of behavioral effects may have been the result of imperfect program implementation or low base rates of intentions and behavior.", "To evaluate the impact of a classroom-based, Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents.\n A two-group randomized control trial with 1,402 male and female students in grades 9 through 11 from 14 secondary schools in Toronto, Canada. Participants were randomly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up. The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine (http://www.smokingzine.org) integrated into a program that included a paper-based journal, a small group form of motivational interviewing, and tailored e-mails.\n Resistance to smoking, behavioral intentions to smoke, and cigarette use were assessed at baseline, postintervention, and three- and six-month follow-up. Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time.\n The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months. The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period.\n The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months. By providing an accessible and attractive method of engaging young people in smoking prevention and cessation, this interactive and integrated program provides a novel vehicle for school- and population-level health promotion.", "The Hutchinson Study of High School Smoking randomized trial was designed to rigorously evaluate a proactive, personalized telephone counseling intervention for adolescent smoking cessation.\n Fifty randomly selected Washington State high schools were randomized to the experimental or control condition. High school junior smokers were proactively identified (N = 2151). Trained counselors delivered the motivational interviewing plus cognitive behavioral skills training telephone intervention to smokers in experimental schools during their senior year of high school. Participants were followed up, with 88.8% participation, to outcome ascertainment more than 1 year after random assignment. The main outcome was 6-months prolonged abstinence from smoking. All statistical tests were two-sided.\n The intervention increased the percentage who achieved 6-month prolonged smoking abstinence among all smokers (21.8% in the experimental condition vs 17.7% in the control condition, difference = 4.0%, 95% confidence interval [CI] = -0.2 to 8.1, P = .06) and in particular among daily smokers (10.1% vs 5.9%, difference = 4.1%, 95% CI = 0.8 to 7.1, P = .02). There was also generally strong evidence of intervention impact for 3-month, 1-month, and 7-day abstinence and duration since last cigarette (P = .09, .015, .01, and .03, respectively). The intervention effect was strongest among male daily smokers and among female less-than-daily smokers.\n Proactive identification and recruitment of adolescents via public high schools can produce a high level of intervention reach; a personalized motivational interviewing plus cognitive behavioral skills training counseling intervention delivered by counselor-initiated telephone calls is effective in increasing teen smoking cessation; and both daily and less-than-daily teen smokers participate in and benefit from telephone-based smoking cessation intervention.", "To test whether high school students' participation in advocacy activities related to the advertising, availability, and use of tobacco in their communities would prevent or reduce their own tobacco use.\n Ten continuation high schools in northern California, randomly assigned to a semester-long program in which students either carried out advocacy activities to counter environmental-level smoking influences in their communities (treatment) or learned about drug and alcohol abuse prevention (control).\n Eleventh and 12th grade high school students; 5 (advocacy) treatment and 5 control schools over 4 semesters from 2000 through 2002.\n Self-reported smoking defined as nonsmokers (those who had never smoked tobacco or those who were former smokers), light smokers (those who smoked <1 pack per week), or regular smokers (those who smoked >or=1 pack per week), and confirmed by carbon monoxide level readings. The following 3 constructs related to social cognitive theory- perceived incentive value, perceived self-efficacy, and outcome expectancies-were assessed.\n There was a significant net change from baseline to the end of the semester (after the intervention) between treatment and control schools for students who were regular smokers, but not for students who were nonsmokers or light smokers. Regular smoking decreased 3.8% in treatment schools and increased 1.5% in control schools (P<.001). Regular smoking continued to decrease at 6 months after the intervention in treatment schools, with a total change in prevalence from 25.1% to 20.3%. Involvement in community-advocacy activities and the 3 social constructs-perceived incentive value, perceived self-efficacy, and outcome expectancies-also showed significant net changes between treatment and control schools (all P values <.01).\n Student engagement in community-advocacy activities that addressed environmental influences of cigarette smoking resulted in significant decreases in regular smoking.", "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.", "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.", "Although many family physicians may discuss smoking cessation with their patients, few do so consistently. A common belief among many physicians is that such efforts will not deter their patients from smoking. Others believe the time commitment required for a successful intervention is excessive. The present study addressed the above issues by examining the effect of a 3- to 5-minute unstructured physician discussion encouraging smoking cessation with family practice patients. Cigarette-smoking patients of two busy family practices in southeast Michigan were randomly assigned to either a control group receiving routine care or an intervention group receiving, in addition to routine care, smoking cessation counseling from their physician. A third comparison group was drawn from smokers in practices not involved in delivering the intervention. Two hundred thirty-eight patients from the intervention group, 178 from the control group, and 47 from the comparison group were followed up with a telephone interview at 6 months. Intervention group patients made significantly more quit attempts than did those in the control group (P less than .001), which was similar to the comparison group. At the 6-month follow-up, 8% of intervention group members, and 4% of both the comparison and control groups reportedly were abstinent from smoking. Among those contacted at the 1-year follow-up, the respective percentages abstinent were 8%, 3%, and 4%. Although these differences in quit rates were not statistically significant, the findings suggest that physicians can positively affect patient smoking cessation. This intervention was feasible in busy family practices, highlighting its generalizability and applicability to other family practice settings in the United States.", "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.", "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.", "Schools in many countries undertake programmes for smoking prevention, but systematic reviews have shown mixed evidence of their effectiveness. Most peer-led approaches have been classroom-based, and rigorous assessments are scarce. We assessed the effectiveness of a peer-led intervention that aimed to prevent smoking uptake in secondary schools.\n We undertook a cluster randomised controlled trial of 10 730 students aged 12-13 years in 59 schools in England and Wales. 29 schools (5372 students) were randomly assigned by stratified block randomisation to the control group to continue their usual smoking education and 30 (5358 students) to the intervention group. The intervention (ASSIST [A Stop Smoking In Schools Trial] programme) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke. Follow-up was immediately after the intervention and at 1 and 2 years. Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake, which was identified at baseline as occasional, experimental, or ex-smokers. Analysis was by intention to treat. This study is registered, number ISRCTN55572965.\n The odds ratio of being a smoker in intervention compared with control schools was 0.75 (95% CI 0.55-1.01) immediately after the intervention (n=9349 students), 0.77 (0.59-0.99) at 1-year follow-up (n=9147), and 0.85 (0.72-1.01) at 2-year follow-up (n=8756). The corresponding odds ratios for the high-risk group were 0.79 (0.55-1.13 [n=3561]), 0.75 (0.56-0.99 [n=3483]), and 0.85 (0.70-1.02 [n=3294]), respectively. In a three-tier multilevel model with data from all three follow-ups, the odds of being a smoker in intervention compared with control schools was 0.78 (0.64-0.96).\n The results suggest that, if implemented on a population basis, the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance.", "To test the effectiveness of a psychosocial strategy of smoking deterence on seventh grade students, the School Health Education Development project implemented peer-led, teacher-led, and expert-led interventions in six Vermont schools. Four additional schools served as control groups. The teacher-led approach reduced the rate of smoking onset and the intention to smoke in the future among highly vulnerable females but not among males. The peer-led approach reduced the behavioral intention to smoke for both sexes but did not affect current smoking behavior. The expert-led approach did not produce favorable effects. Both the peer-led and teacher-led interventions had positive, though not significant, effects on student perception of locus of control. In the control schools, females experienced higher levels of smoking onset than males. Generally, the study points toward further development of a teacher-led approach to smoking deterence based on the theory of adolescent psychosocial development and the principle of continuous reinforcement.", "This article describes preliminary findings of an experimental, randomized, three-group, controlled design examining the effectiveness of a smoking cessation intervention for pregnant teens. The three groups are: Teen FreshStart with a buddy program (TFSB), a Teen FreshStart program (TFS) without peer support, and the Usual Care (UC) control group. Forty-six subjects completed the post-intervention assessment of smoking status. The TFSB group consistently achieved greater smoking cessation across all measures when compared to the subjects in the other two groups. These results indicate that the use of peer support may be an effective adjunct in smoking cessation programs for pregnant adolescents.", "This paper reports findings from a longitudinal study that evaluated the accumulated effect of three consecutive mass media campaigns using provocative and dissonance arousing appeals to prevent cigarette smoking by adolescents. In the spring of 1992, all eligible adolescents aged 14 and 15 in one intervention county (N = 4898) and one control county (N = 5439) in Norway were included in the study, and were followed until they were 17 and 18 years of age in 1995. Only students who completed questionnaires both in 1992 and 1995 were included in the analyses. Among the non-smokers at baseline, a significantly lower proportion of adolescents of both genders had started to smoke in the intervention county compared to the proportion in the control county. Among those who were smokers at baseline, significantly more girls in the intervention county had stopped smoking than in the control county, while no significant difference between the counties was detected among boys. Our findings suggest that provocative and dissonance arousing appeals that create affective reactions and lead to interpersonal communication should be given more attention in campaigns designed to influence adolescent smoking. However, such appeals may easily produce negative reactions and the normative context should be thoroughly considered when using such appeals in future interventions.", "The present randomized controlled trial tested the effectiveness of a behavioral counseling program for reducing children's exposure to environmental tobacco smoke (ETS). Counseling was delivered by clinic staff as part of well-child health care services in a community clinic setting. A total of 150 mothers with children aged 4 years or younger were recruited. Parent-reported and children's urinary cotinine measures of ETS exposure were obtained at baseline, 3 months, 6 months (post-test), and 12 months (follow-up). Saliva samples were obtained from mothers who reported quitting smoking, for objective verification by thiocyanate analysis. After baseline, mothers were randomly assigned to a measures-only control condition or an intervention consisting of seven behavioral counseling sessions over 6 months. Counseling included behavioral contracting, self-monitoring, problem solving, and positive reinforcement. Results indicated acceptable test-retest reliability and validity of measures. Parent-reported measures indicated that, in both groups, children's exposure to their mothers' tobacco smoke in the home and to all tobacco smoke declined steeply from baseline to 6 months post-test, and remained essentially level during follow-up. Mothers' smoking rates followed the same pattern. Children's urinary cotinine concentrations did not show significant change over time in either group. Findings on the fidelity of treatment implementation suggest that the structure and funding of the community clinic health care system and associated staff turnover and training issues resulted in participants receiving a less efficacious intervention than in our past efficacy trials. Implications for future effectiveness trials are discussed.", "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.", "The efficacy of contingency-management (CM) and motivational enhancement therapy (MET) for college student smoking cessation was examined.\n Nontreatment-seeking daily smokers (N = 110) were randomly assigned to 3 weeks of CM versus noncontingent reinforcement (NR) and to three individual sessions of MET versus a relaxation control in a 2 x 2 experimental design. Expired carbon monoxide (CO) samples were collected twice daily for 3 weeks. Participants earned 5 US dollars for providing each sample; additionally, those randomized to CM earned escalating monetary rewards based on CO reductions (Week 1) and smoking abstinence (Weeks 2-3).\n Compared with NR, CM resulted in significantly lower CO levels and greater total and consecutive abstinence during the intervention. Those in the CM and MET groups reported greater interest in quitting smoking posttreatment, but rates of confirmed abstinence at follow-up were very low (4% at 6-month follow-up) and did not differ by group.\n Findings support the short-term efficacy of CM for reducing smoking among college students. Future research should explore enhancements to CM in this population, including a longer intervention period and the recruitment of smokers who are motivated to quit.", "We describe the results of a randomized controlled study on the efficacy of a smoking prevention program based on behavioral methods (Waterloo Smoking Prevention Program 1, adapted). 792 children of 12-13 years of age from the Health District of Rozzano (MI) were the study base. The program was delivered directly by voluntary teachers during school classes. Two follow-up, at 18 and 36 month from the end of the program were conducted using self-administered questionnaire and telephonic interviews. At 36 months the proportion of non-smokers was higher in the intervention group (55% vs 44%; OR (adjusted for clustering) = 1.7; p = .03) and that of regular (at least one cigarette a week) smokers lower (22% vs 39%) than in the control group. We found no difference of effect between males and females students. Social pressure associated with starting to smoke (friends, sibsters, parents smokers) measured before intervention had no demonstrable influence on efficacy. We propose this kind of intervention for Italian students as an effective and low-cost program, even though more research is needed to maintain effectiveness of these kind of programs beyond adolescence.", "Skills intervention to prevent cigarette smoking was evaluated with 689 adolescents. At 24-month follow-up, youths who received health information and skills intervention had lower intentions to smoke and less cigarette use than youths who received health information alone and youths who received no intervention. Conclusions about the effects of skills intervention are strengthened by the common preparation and random assignment of intervention leaders and by process measurement data.", "Motivational interviewing techniques have been minimally researched as a function of a teenage smoking intervention. The present study examined the efficacy of a theory-based motivational tobacco intervention (MTI).\n A randomized two-group design was used to compare 6-month post-baseline quit and reduction rates among teenagers who received the MTI with those who received brief advice or care as usual. Participants were smokers aged 14 to 19 years (N = 75) who presented for treatment in a university-affiliated hospital emergency department (ED). Motivational interviewing techniques were used by trained providers to facilitate individual change; stage-based take-home materials also were provided.\n Similar to past clinic-based studies of motivational interviewing with teenage smokers, our study found negative results in terms of intervention efficacy for cessation. Six-month follow-up cessation rates were nonsignificant--two teenagers quit smoking. Among teenagers who were available at follow-up, a medium effect size (Cohen's h = .38) was found for reduction and a large effect size (Cohen's h = .69) was found for percentage reduction, although these results also were not statistically significant.\n Although the major findings of this study were not significant, the reductions in tobacco use suggest that motivational interviewing may be a clinically relevant counseling model for use in teenage smoking interventions. However, many questions remain, and the current literature lacks studies on trials with significant outcomes using motivational interviewing in smoking cessation. Additionally, more research is needed to examine the suitability of the ED for MTI-type interventions." ]

[ "15671970" ]

[ "Graduated driver licensing in Utah: is it effective?" ]

[ "We seek to examine the effectiveness of the graduated driver licensing system in Utah by determining whether crash rates of 16-year-old drivers decreased after graduated driver licensing implementation.\n We studied 16-year-old-driver crashes using statewide motor vehicle crash data probabilistically linked to emergency department (ED), hospital inpatient, and driver licensure data for 1996 to 2001. Outcomes examined included overall crash rates, nighttime crashes, crash severity indicators (eg, noninjury crash, injury crash, ED crash, inpatient crash, fatal crash), seat belt usage, licensure status, and citations. Rate ratios (RR), chi 2 tests, and interventional time series analyses were used to assess changes before and after graduated driver licensing implementation.\n There were 27,304 16-year-old-driver crashes during the study period. The overall crash rate per 1,000 licensed 16-year-old drivers decreased by 5% (RR 0.95; 95% confidence interval [CI] 0.92 to 0.97), and a time-series analysis showed a reduction of 0.8 (SD 0.39) crashes per month per 1,000 licensed drivers after graduated driver licensing implementation (1996 to 1999 versus 1999 to 2001). The nighttime crash rate did not change (RR 0.91; 95% CI 0.78 to 1.04), and there was no association between crash severity and graduated driver licensing implementation ( P =.096). Reported seat belt usage increased by 6.3%, and few graduated driver licensing citations were issued by law enforcement.\n The results suggest that graduated driver licensing may have contributed to a reduction in young driver crashes, but the effects were minimal compared with those shown in many other graduated driver licensing evaluations." ]

[ "9691103", "15017504", "8536887", "9692692", "8881815", "15709986", "12135030", "11922560", "15095852", "9616309", "10333200", "9301500", "8078529" ]

[ "A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group.", "Budesonide versus mesalamine for maintaining remission in patients refusing other immunomodulators for steroid-dependent Crohn's disease.", "Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Canadian Inflammatory Bowel Disease Study Group.", "Oral budesonide as maintenance therapy in Crohn's disease--results of a 12-month study. Global Budesonide Study Group.", "Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.", "Budesonide as maintenance treatment in Crohn's disease: a placebo-controlled trial.", "Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States.", "Budesonide and mesalazine in active Crohn's disease: a comparison of the effects on quality of life.", "Budesonide versus prednisolone for the treatment of active Crohn's disease in children: a randomized, double-blind, controlled, multicentre trial.", "Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease. The Budesonide Study Group.", "Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group.", "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." ]

[ "Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both.\n In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index.\n In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02).\n In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.", "To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease.\n Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).\n There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores.\n Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.", "Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease.\n In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points.\n Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups.\n Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up.", "Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease.\n In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time.\n There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096).\n In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.", "To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD).\n Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment.\n Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups.\n 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.", "To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon.\n In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration].\n Median time to relapse was 360 days for budesonide patients; 169 days for placebo patients (P = 0.132). No significant differences were seen between groups in relapse rates at 1 year. Budesonide was safe and well tolerated, with a similar adverse events profile to placebo.\n Patients treated with budesonide 6 mg once daily had a trend towards a prolonged time to relapse and lower CDAI scores compared with patients treated with placebo, but relapse rates were not significantly different at the 1-year end point.", "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.", "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.", "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.", "The relapse rate after steroid induced remission in Crohn's disease is high.\n To test whether oral pH modified release budesonide (3 x 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse.\n In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 x 1 mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year.\n Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group.\n Oral pH modified release budesonide at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease.", "Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence.\n A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed.\n Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial.\n Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery.\n Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used.\n The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient.\n The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.).\n Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease.", "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." ]

[ "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." ]

[ "2889518", "2730380", "7501140", "7611638", "3902184" ]

[ "A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group.", "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.", "A double-blind, placebo-controlled trial of amantadine for the treatment of fatigue in patients with the post-polio syndrome.", "Amantadine therapy for fatigue in multiple sclerosis." ]

[ "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.", "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.", "Because amantadine has been shown to reduce fatigue in patients with multiple sclerosis, we performed a double-blind, placebo-controlled study to assess its efficacy in the disabling symptom of post-polio fatigue. Twenty-three patients completed six weeks of therapy. Fatigue was measured by the patients using visual analogue scales (twice per day) and numerical fatigue severity scales (once per week) and by overall impression (at end of therapy). Formal neuropsychological testing and serum drug levels were performed to assess compliance. On all measures, no significant difference was found between treatment and placebo groups. Fifty-four percent of patients given amantadine and 43% given placebo reported a decrease in fatigue; however, the visual analogue scales and fatigue severity scales failed to reflect any improvement. Several patients in the treatment group elected to continue amantadine therapy after the study was completed. Our findings suggest that amantadine is not significantly better than placebo in reducing the sensation of fatigue in post-polio syndrome, and that the measures we employed were insensitive to capture the subjective response experienced by a few patients.", "We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5% unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects." ]

[ "11880065", "14970093", "11295408", "10190914", "16566424", "9892331", "2085989", "16392777", "2487304", "17127226", "10440621", "3846198", "7324942", "6565475", "16765169", "16326693", "12581547", "3288946" ]

[ "Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, double-blind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens.", "Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial.", "Treatment of lower urinary tract infection in pregnancy.", "Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.", "[A study of non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections in women (the NAPRUTI study)].", "Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.", "Fosfomycin trometamol versus netilmicin in children's lower urinary tract infections.", "Acute uncomplicated lower urinary tract infections in general practice: clinical and microbiological cure rates after three- versus five-day treatment with trimethoprim.", "[Acute cystourethritis during pregnancy].", "A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.", "Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group.", "Single-dose versus conventional therapy of urinary tract infections in female adolescents.", "The length of antimicrobial therapy in upper vs. lower urinary tract infection of childhood.", "Single-dose treatment of uncomplicated urinary tract infections in children.", "Effectiveness of ciprofloxacin prophylaxis in preventing bacteriuria caused by urodynamic study: a blind, randomized study of 192 patients.", "Effective duration of antimicrobial therapy for the treatment of acute lobar nephronia.", "Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women.", "Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children." ]

[ "To compare the efficacy and safety of single-dose and 3-day fluoroquinolone treatment of uncomplicated urinary tract infection (UTI).\n Adult women with acute uncomplicated UTI were randomized to receive either a single dose of gatifloxacin (400 mg), 3 days of gatifloxacin (200 mg daily), or 3 days of ciprofloxacin (100 mg twice daily). Patients were assessed at four points during the study: before treatment (within 48 hours before the initiation of the study medication), at the end of treatment (by telephone contact on day 3), and twice after treatment completion (5 to 9 days after treatment [test-of-cure visit] and 29 to 42 days after treatment [only patients with a bacteriologic response of eradication at the test-of-cure visit]).\n The bacterial eradication rate for the single-dose gatifloxacin, 3-day gatifloxacin, and 3-day ciprofloxacin groups was 90%, 95%, and 89%, respectively; the clinical efficacy rate was 93%, 95%, and 93%, respectively, for microbiologically assessable patients at the test-of-cure visit. Eradication of the most common uropathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, was achieved with gatifloxacin and ciprofloxacin. Single-dose gatifloxacin was equivalent to 3-day ciprofloxacin in both microbiologic and clinical efficacy.\n Single-dose and 3-day gatifloxacin were microbiologically and clinically equivalent to 3-day ciprofloxacin for the treatment of acute UTI among women. Single-dose gatifloxacin may offer advantages over 3-day fluoroquinolone therapy for uncomplicated UTI by decreasing secondary use of medical resources and improving patient compliance.", "The optimal duration of antibiotic therapy in older patients with uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim of this randomized controlled double-blind noninferiority trial was to compare the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for uncomplicated symptomatic UTI in older women.\n A total of 183 women at least 65 years of age with acute uncomplicated UTI were recruited from ambulatory clinics and hospital acute care units. Patients with pyelonephritis, contraindications to fluoroquinolones, recent use of antibiotics, urinary tract abnormalities and diabetes mellitus were excluded. Women were randomly assigned to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication, clinical improvement and occurrence of adverse events were determined 2 days after completion of treatment, and occurrence of reinfection or relapse were determined 6 weeks after completion of treatment. Bacterial eradication and relapse were determined by urine culture. Double-blind procedures were maintained throughout data collection.\n The proportion of patients with bacterial eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93% (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly lower in the 3-day group.\n These results suggest that a 3-day course of antibiotic therapy is not inferior to a 7-day course for treatment of uncomplicated symptomatic UTI in older women, and that the shorter course is better tolerated.", "Urinary tract infection (UTI) is a common complication of pregnancy. Approximately 20--40% of women with asymptomatic bacteriuria will develop pyelonephritis during pregnancy. All pregnant women, therefore, should have their urine cultured at their first visit to the clinic. In a clinical study comparing single-dose treatment with 3 g fosfomycin trometamol versus a 3-day course of 400 mg ceftibuten orally, the inclusion criteria were acute symptomatic lower UTI (acute cystitis), significant bacteriuria (> or =10(3) CFU/ml), pyuria and confirmed pregnancy. Excluded were patients with asymptomatic bacteriuria or acute pyelonephritis. Predisposing factors comprised a history of recurrent UTI, diabetes mellitus, analgesic nephropathy, hyperuricaemia or Fanconi's syndrome. Escherichia coli was the most frequently isolated pathogen in both groups. Therapeutic success (clinical cure and bacteriological eradication of uropathogens) was achieved in 95.2% of the patients treated with fosfomycin-trometamol versus 90.0% of those treated with ceftibuten (P, non-significant). The treatment of acute cystitis in pregnant women using a single-dose of fosfomycin trometamol was equally effective as the 3-day course of oral ceftibuten. Both regimens were well tolerated with only minor adverse effects. Long-term chemoprophylaxis should be suggested in patients with recurrent UTI or following acute pyelonephritis during pregnancy.", "We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. Study design: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization.\n No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy.\n We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.", "Patient enrolment in the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study was started in September 2005. In this study of women with recurrent urinary-tract infections we aim to investigate the effect of 12 months of non-antibiotic prophylaxis in comparison with antibiotic prophylaxis on the rate of recurrence of urinary-tract infections and the development of antibiotic resistance. The study consists of two interlinked, randomised, clinical non-inferiority trials. In one trial, 280 premenopausal women will receive either cranberry capsules (twice daily 500 mg) or standardised antibiotic therapy (once daily 480 mg trimethoprim-sulfamethoxazole). In the other trial, 280 postmenopausal women will receive either oral lactobacilli (twice daily a capsule with > 10(9) colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) or standardised antibiotic therapy. Non-inferiority of non-antibiotic prophylaxis would be attractive given its potential to reduce the prevalence of microbial resistance to antibiotics significantly.", "There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI).\n In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin.\n There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens.\n In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.", "Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36-48 h after a single oral dose of 1-2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever (less than 38 degrees C), erythrocyte sedimentation rate (less than 25 mm/l h) and C-reactive protein (less than 20 micrograms/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and children.", "Epidemiological studies indicate that acute uncomplicated urinary tract infections (UTI) in women can be successfully treated with short treatment regimens. However, the findings from the literature do not match experiences in daily practice.\n A randomised, controlled trial evaluating the microbiological and clinical (self-reported) cure rates of a three-day vs. five-day treatment regimen with trimethoprim for UTI in women.\n No statistically significant difference in bacteriological cure rate was found between the three-day and five-day regimen. One day after the shorter regimen 44% of women considered themselves as 'not-recovered' due to persistence of the symptoms compared with 35% after the five-day treatment (p > 0.05). Three days after therapy these percentages were 30 and 25% respectively.\n The relatively high percentage of persistent symptoms one day after the three-day regimen might be responsible for general practitioners believing that short regimens are not successful. It is therefore advisable that if urine samples are controlled to wait at least three days after finishing treatment.", "A prospective study was carried out in 103/863 obstetric patients with cystitis characterized by urinary urgency and frequency, dysuria, pyuria and suprapubic discomfort in the absence of systemic symptoms such as fever and costovertebral angle tenderness. The association of symptomatic lower urinary tract infection with low-count bacteriuria (10(2)-10(5) UFC/mL of urine) was present in all the patients. The incidence of cystourethritis was about 12%, most of the infections occurred at the first trimester. To learn whether a multiple-dose of nitrofurantoin or ampicillin is safe and effective therapy for acute uncomplicated urinary tract infections, 103 symptomatic pregnant women were randomly grouped to receive oral nitrofurantoin (100 mg t.i.d.) or ampicillin (500 mg t.i.d.) for five days. Seventeen patient were excluded since they did not return for follow-up. Escherichia coli was isolated in 67% of infections. Overall cure varied from 87% to 89%, without any great differences between the regimens. Nine patients had asymptomatic bacteriuria in the course of pregnancy, four developed acute pyelonephritis and one of them had abnormal intravenous pyelogram.", "The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.", "Urinary tract infection (UTI) is a common illness, with > or =30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with > or =7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group (P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.", "A randomized, prospective study was done to assess the efficacy of single-dose nu conventional treatment of acute urinary tract infection (UTI) in female adolescents. Thirty-one 12- to 18-year-old female adolescents with symptoms of an acute UTI and a urine culture with greater than 10(5) organisms were treated with amoxicillin, either as a 3.0-g single dose or 250-mg three times daily for ten days. Urine cultures obtained three days after completing therapy in each group, showed bacteriologic cure rate of 69% (11/16) with single-dose treatment compared with a cure rate of 87% (13/15) in the conventional treatment group (P = .23). When patients with resistant organisms were excluded, the cure rate was 85% in both groups. Complete symptom resolution in less than two days after commencing treatment occurred in 36% of single-dose group nu none of the patients in the conventional-dose group. The finding has not been previously reported in single-dose trials. Candida vaginitis occurred in 20% of the conventional-dose group nu none of the single-dose group. All patients in the single-dose group kept their first scheduled follow-up appointment, whereas 40% in the conventional group required reminders and rescheduling. Perfect compliance with the medication regimen was reported by 27% of the patients taking ten days of medicine. Although single-dose cure rates may not be superior to conventional-dose rates, the advantages of single-dose treatment include increased compliance with medication and follow-up, decreased side effects, and more rapid resolution of symptoms.", "235 infants and children were randomized to a 10-day and 42-day treatment group and followed-up for 12 months after their first urinary tract infection. The anatomical level of each symptomatic infection was determined using simple laboratory criteria. The two regimens prescribed were equally effective in eradicating the infection, but after the discontinuation of the 10-day treatment with sulfafurazole, 17 (23%) of 73 patients with their upper urinary tract infection experienced a recurrence within one month, as compared to only one (1) of 76 subjects in the 42-day therapy group. After the phase of early recurrence, there was no difference in recurrence rate between these groups. The early recurrences were associated with the patient's early age and a short duration of symptoms before therapy. The recurrence rate of first lower UTI after 10-day therapy was significantly lower than that after 42-day treatment. The duration of antimicrobial therapy for childhood urinary tract infection should be adjusted according to the patient's age and the anatomical level of the infection. 10-day treatment may not be sufficient to prevent early recurrence of pyelonephritic infections in infants under 6 months of age.", "Thirty-six girls, aged two to 17 years, with culture-proven, acute, uncomplicated lower urinary tract infections and without signs or symptoms of upper urinary tract infection, were randomized to receive either single-dose amoxicillin or conventional therapy for ten days. Twenty-six patients completed the study, ten in the single-dose group and 16 in the conventional therapy group. The patients treated with single-dose therapy had cure rates (70% vs 75%), relapse rates (30% vs 25%), and reinfection rates (0% vs 12%) comparable to those of conventionally treated patients. A significant difference in the induction of resistant organisms was seen between treatment groups (P less than .05). All single-dose relapses were due to failure to clear a sensitive organism from the urinary tract. All relapses on conventional therapy resulted from an initially sensitive organism becoming resistant to amoxicillin during treatment. Single-dose antibiotic therapy of uncomplicated urinary tract infections in children is effective in patients with culture-proven infections selected by clinical criteria, and appears to be safe when combined with conscientious long-term follow up and radiographic evaluation. Single-dose therapy offers the advantage of selecting significantly fewer resistant organisms from the gut flora than do conventional antibiotic regimens.", "To determine the efficacy of prophylactic ciprofloxacin in preventing urinary tract infections caused by urodynamic study (UDS).\n A total of 210 patients presenting for UDS during a 16-month period were offered enrollment in the study. A clean-catch midstream urine sample was taken 24 hours before and 48 to 72 hours after the procedure and after microscopic examination and culture were done. All patients underwent a standard UDS. The 192 patients who had sterile urine before intervention were included in the study. Randomly, 98 of the 192 patients were orally given 500 mg of ciprofloxacin 1 hour before the urodynamic intervention and 94 were not given anything. The patients who were found to have significant bacteriuria after UDS were followed up and treated properly.\n Eighteen patients (8.6%) who had significant bacteriuria in the urine culture before UDS were excluded from the study. The rate of significant bacteriuria in the urine culture after UDS was 7.3% overall, 1% in the prophylaxis group, and 14% in the controls, a significant difference (P = 0.002). The most common uropathogen was Escherichia coli (57%). Three independent risk factors were identified: not giving antibiotic prophylaxis before UDS; antibiotic use in the preceding month; and the presence of pyuria before UDS.\n Urinary tract infections after UDS decreased from 14% to 1% with a single dose of ciprofloxacin 500 mg orally before UDS. We recommend antibiotic prophylaxis for patients undergoing a UDS.", "Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen.\n Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures.\n A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>10(5) colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course.\n A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.", "Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the first choice for empiric therapy of acute uncomplicated urinary tract infection (UTI) in women. In areas where resistance to TMP/SMX is known to be high, ciprofloxacin and other fluoroquinolones are recommended as first-line choices for the empiric therapy of UTI.\n This study compared the efficacy and safety profile of once-daily extended-release ciprofloxacin 500 mg (referred to hereafter as ciprofloxacin QD) with those of conventional ciprofloxacin 250 mg BID, each administered orally for 3 days, in the treatment of uncomplicated UTI in women.\n In this multicenter, prospective, randomized, double-blind, double-dummy, Phase III trial, adult women with clinical signs and symptoms of acute uncomplicated UTI, pyuria, and a positive pretherapy urine culture (>/=10(5) colony-forming units/mL) received ciprofloxacin QD or ciprofloxacin BID. Bacteriologic and clinical outcomes were assessed at the test-of-cure visit (4-11 days after completion of therapy) and the late follow-up visit (25-50 days after completion of therapy).\n The intent-to-treat population consisted of 891 patients (444 ciprofloxacin QD, 447 ciprofloxacin BID); 422 patients were evaluable for efficacy (199 ciprofloxacin QD, 223 ciprofloxacin BID). At the test-of-cure visit, bacteriologic eradication was achieved in 94.5% (188/199) of the ciprofloxacin QD group and 93.7% (209/223) of the ciprofloxacin BID group (95% CI, -3.5 to 5.1). Clinical cure was achieved in 95.5% (189/198) of the ciprofloxacin QD group and 92.7% (204/220) of the ciprofloxacin BID group (95% CI, -1.6 to 7.1). Bacteriologic and clinical outcomes at the late follow-up visit were consistent with the test-of-cure findings. The rate of eradication of Escherichia coli, the most prevalent organism, was >97% in each treatment group. Rates of drug-related adverse events were similar with the once- and twice-daily ciprofloxacin regimens (10% and 9%, respectively).\n Extended-release ciprofloxacin 500 mg given once daily for 3 days was as effective and well tolerated as conventional ciprofloxacin 250 mg given twice daily for 3 days in the treatment of acute uncomplicated UTI in women.", "One hundred thirty-two children with acute urinary tract infection were randomly assigned to receive trimethoprim-sulfamethoxazole in one dose, two doses daily for 3 days or two doses daily for 7 days. The patient characteristics, etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups. There was no significant difference in bacteriologic cure rates for the single dose regimen (93%) and multidose regimens (96%). The difference in rates of recurrent urinary tract infection between the single dose (20.5%) and 3-day (5.6%) and 7-day (8%) regimens was statistically significant (P = 0.033). A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection." ]

[ "1751442", "8399011", "9875920", "2223682", "9141579", "12946338", "8476803", "11408301" ]

[ "Doppler flow velocity waveform analysis in high risk pregnancies: a randomized controlled trial.", "The effect of introduction of umbilical Doppler recordings to obstetric practice.", "A randomized, controlled trial of computerized physiologic trend monitoring in an intensive care unit.", "Randomized comparison of routine vs highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies.", "Randomised controlled trial of cardiotocography versus umbilical artery Doppler in the management of small for gestational age fetuses.", "A randomised controlled trial of admission electronic fetal monitoring in normal labour.", "Randomised comparison of routine versus highly selective use of Doppler ultrasound in low risk pregnancies.", "Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population." ]

[ "To test whether the introduction of Doppler waveform analysis into the ultrasound department of a tertiary level hospital reduces neonatal morbidity and improves obstetric management.\n A randomized controlled trial.\n Department of Ultrasound, King Edward Memorial Hospital, Perth, Western Australia.\n 505 women with pregnancy abnormalities referred to an ultrasound department for fetal investigation during the third trimester.\n Continuous wave Doppler studies of umbilical and uteroplacental arterial circulations. Results were revealed to patients and clinicians.\n Principal end point was the duration of neonatal stay in hospital; other end points included the number and type of fetal heart rate monitoring studies, obstetric interventions, frequency of fetal distress, birthweight, Apgar scores and need for neonatal intensive care.\n There was no effect on the duration of neonatal stay in hospital. Small trends in obstetric management were observed with study group patients having fewer contraction stress tests, less likelihood of antepartum fetal distress, and more likelihood of fetal distress after induction of labour leading to emergency caesarean section. Depressed Apgar scores were more frequent in the study group.\n Introduction of Doppler waveform studies did not result in reduced neonatal morbidity but did have a small effect on obstetric management. For each institution the role of Doppler studies in late pregnancy will be influenced by the usage of other tests of fetal welfare already entrenched in clinical practice.", "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.", "To assess whether the provision of computerized physiologic trend data could improve outcome in newborn infants requiring intensive care.\n Randomized, controlled trial, with subsidiary questionnaire studies.\n Tertiary neonatal intensive care unit with 12 intensive care cots.\n All infants admitted between January 1991 and September 1993 who were < or =32 wks gestation or >32 wks gestation, and ventilated for >4 hrs or asphyxiated.\n Randomization to one of four groups for first 7 days of life: A) no display of trend data; B) continuous display of trend data; C1) alternating 24-hr display of trend data, starting with display in first 24 hrs; and C2) alternating 24-hr display of trend data, starting with no display in first 24 hrs.\n The short-term effects of monitoring on patient outcome was judged by volume of colloid given, number of blood gases taken, and by measurement taken from cranial Doppler ultrasound. Medium-term measures included time ventilated, time given supplemental oxygen, death, time to death or discharge, and cranial ultrasound at discharge. Long-term outcome was assessed by neurodevelopmental status at age 1 to 4 yrs of age. Staff and parent questionnaires assessed their respective attitudes to the introduction of this technology. None of the patient outcome measures, short-, medium-, or long-term, demonstrated any significant benefit from the provision of computerized physiologic trend monitoring. Staff questionnaires demonstrated an acceptance of the system and an improved understanding of neonatal physiology as a result of computerized physiologic trends. Parent questionnaires demonstrated increased anxiety caused by the system in 11% of parents, although only 1% of parents continued to have concerns if the system were able to help their child.\n A randomized, controlled trial was unable to demonstrate any benefit to patients resulting from the introduction of a computerized physiologic trend monitoring system. Benefits of the system have been recognized, however, in subsidiary studies, staff education, and research studies.", "To compare routine versus highly selective use of Doppler ultrasound and biophysical scoring in higher risk pregnancy.\n A pragmatic randomized trial.\n St James's University Hospital, Leeds.\n 500 pregnant women at high risk of intrauterine growth retardation or still birth.\n Regular monitoring with biophysical profile assessment and Doppler velocity waveform recording in umbilical and uteroplacental arteries. Results immediately available to clinicians.\n Gestational age at delivery, obstetric intervention rates and short-term neonatal morbidity.\n Risk factors were distributed very evenly between the 250 patients in the study and control groups respectively. A total of 902 biophysical profile and Doppler assessments were done in the 250 study group patients and only in 12 patients in the control group. In the study group, absent end-diastolic flow was found in only 2.7% of all 902 measurements. A persistently abnormal biophysical score was always associated with absence of end-diastolic flow. The mean gestational age at induction of labour was statistically and clinically similar in the two groups and there was no overall statistically significant difference in intervention rates between the two groups. There was a statistically significant lower frequency of depressed 5-min Apgar scores in the study group. Serious neonatal morbidity was also statistically significantly more common in the control group than in the study group.\n The use of Doppler ultrasound in higher risk pregnancies does not lead to an increase in iatrogenic preterm delivery. The total rate of positive tests on Doppler ultrasound is very low and persistently abnormal biophysical scores are unlikely to be found in patients where umbilical end-diastolic blood flow is present. Surrogate measures for fetal damage seem to be improved when clinicians have access to Doppler ultrasound assessments.", "To compare the impact on use of resources in the management of small for gestational age babies using Doppler ultrasound versus cardiotocography.\n A randomised controlled trial.\n A large district general hospital delivering 5500 to 6000 infants each year, 30% to 35% of which are to women of Pakistani origin.\n One hundred and fifty women delivered of small for gestational age infants.\n Primary outcome measures were length of hospital inpatient stay and induction of labour rates. Secondary outcome measures included caesarean section rates and length of stay on neonatal unit.\n The use of Doppler reduced average hospital inpatient stay from 2.5 days to 1.1 days, compared with cardiotocography (P = 0.036). There was no effect on induction of labour rates or caesarean section rates. There was no significant difference in length of stay on the neonatal unit (P = 0.33). There was a reduction in monitoring frequency and fewer hospital antenatal clinic visits.\n The use of Doppler ultrasound to manage small for gestational age infants reduces the use of resources, compared with cardiotocography.", "To test the hypothesis that the use of admission Electronic Fetal Monitoring (EFM) for healthy pregnant women in spontaneous labour would result in an increase in continuous EFM when compared to women who have had no admission EFM.\n A randomised controlled trial.\n The Midwives Birth Unit in Glasgow Royal Maternity Hospital, a major urban teaching hospital with approximately 5000 births per year.\n Healthy pregnant women admitted in normal labour, deemed low risk based on the midwives' birth unit admission criteria.\n Women were randomly allocated either to receive a routine 20-minute period of EFM at the time of admission (control group), or to receive no routine admission EFM (study group).\n Primary study outcomes, use of continuous EFM; and use of EFM additional to the admission test. Secondary outcomes: artificial rupture of membranes, use of fetal scalp electrode, fetal blood sample, syntocinon, epidural analgesia, number of vaginal examinations, rate of transfer to labour ward, and reason for transfer.\n There was no statistically significant difference between the groups for use of continuous monitoring, but significantly more women in the control group did receive additional EFM. There was no statistically significant difference between groups for any of the interventions studied.\n The use of admission EFM did not in itself lead to a cascade of intervention. Other factors including setting of care and philosophy of caregivers may have an effect on the rate of intervention in labour.", "To help answer the question: should Doppler ultrasound of the umbilical circulation be made available to all pregnant women as part of their routine antenatal care?\n A randomised trial.\n St James's University Hospital, Leeds.\n 2025 low risk primigravid women.\n Obstetric intervention rates and short term neonatal morbidity.\n The incidence of abnormal Doppler was low (1.7%) with complete absence of end diastolic flow in only 0.3% of cases. No significant differences could be demonstrated between control and study women in any of the outcomes measured.\n This study did not demonstrate any benefit or harm from Doppler ultrasound as a routine screening test for all low risk women, whereas our previous studies have suggested that it is useful in high risk pregnancies. Any marginal returns on extending access to Doppler ultrasound from high risk to all women must be small. Since this test has excellent performance characteristics (sensitivity and specificity) for the prediction of fetal hypoxia and acidosis our results call into question the cost to benefit ratio of all tests designed to predict these outcomes in low risk women.", "To compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population.\n Randomised controlled trial.\n Obstetric unit of teaching hospital\n Pregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour.\n Women were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour.\n The primary outcome measure was umbilical arterial metabolic acidosis. Secondary outcome measures included other measures of condition at birth and obstetric intervention.\n There were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65).\n Compared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery." ]

[ "11251497", "2406656", "12092017", "7819846", "8924098", "2927328", "8494832", "16154062", "2406169" ]

[ "Team midwifery care in a tertiary level obstetric service: a randomized controlled trial.", "A randomized trial of nurse-midwifery prenatal care to reduce low birth weight.", "Traditional care of the perineum during birth. A prospective, randomized, multicenter study of 1,076 women.", "Midwife managed delivery unit: a randomised controlled comparison with consultant led care.", "A randomized, controlled trial of nurse-midwifery care.", "The 'Know Your Midwife' scheme--a randomised trial of continuity of care by a team of midwives.", "Simulated home delivery in hospital: a randomised controlled trial.", "Midwifery care measures in the second stage of labor and reduction of genital tract trauma at birth: a randomized trial.", "Evaluation of the home-visiting system for women with threatened preterm labor: results of a randomized controlled trial." ]

[ "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.", "In a randomized, controlled trial in five regional centers with state health department clinics, 1458 women at high risk for low birth weight (LBW) outcome received either prenatal interventions provided by nurse-midwives and nurses under their supervision or the standard high-risk prenatal care provided by obstetricians. The intervention administered by the nurse-midwives included patient education to identify the signs and symptoms of preterm labor, activity counseling in response to monitoring of the cervix by frequent examinations, stress reduction by enhancing social support, nutrition counseling with emphasis on weight gain, and substance-abuse counseling. For women in the control group, care was provided by obstetricians according to local standards for the management of high-risk pregnancies. We hypothesized that the LBW rate among live births to women who had received care from nurse-midwives would be lower than that in the control group. Although the LBW rate was lower in the intervention group than in the control group, the observed difference was not statistically significant. Race was not prespecified as a possible effect modifier, but examination of the data post hoc suggested that black women at high statistical risk of giving birth to an LBW infant may have derived benefit from the program. Although the results do not suggest any striking advantage of the nurse-midwifery intervention over standard obstetric care for women at high statistical risk of having an LBW infant, neither do they suggest any disadvantage. Nurse-midwives could provide care to certain populations of high-risk women and facilitate future coverage of these presently underserved populations.", "To investigate the influence of the traditional hands-on versus the innovative hands-poised method on the risk of perineal trauma during vaginal delivery and on neonatal outcomes.\n In a prospective, randomized, multicenter study, 1,161 of 1,505 women giving birth at the Departments of Obstetrics and Gynecology of the University Hospital of Vienna and Semmelweis Women's Hospital, Vienna, between February and September 1999, were randomized into the trial. In the hands-on method, the left hand of the midwife puts pressure on the infant's head, and the right hand is placed against the perineum. In the hands-poised method, the midwife guides the parturient through the birth without touching the perineum, prepared to apply light pressure on the infant's head.\n One hundred eighty-seven of 574 women (32.5%) in the hands-on group and 180 of 502 women (35.8%) in the hands-poised group experienced perineal tears (P = .5). Sixteen women (2.7%) treated with the hands-on method developed third-degree perineal tears as compared with five women (0.9%) treated with the hands-poised method (P < .05). In the hands-on group, 103 women (17.9%) underwent episiotomy as compared with 51 cases (10.1%) in the hands-poised group (P < .01). No significant differences in neonatal outcomes were observed between the two groups.\n Our data suggest that a policy of hands-poised care is more suitable for preserving the perineum during birth and is a safe and effective birthing alternative for women.", "To examine whether intrapartum care and delivery of low risk women in a midwife managed delivery unit differs from that in a consultant led labour ward.\n Pragmatic randomised controlled trial. Subjects were randomised in a 2:1 ratio between the midwives unit and the labour ward.\n Aberdeen Maternity Hospital, Grampian.\n 2844 low risk women, as defined by existing booking criteria for general practitioner units in Grampian. 1900 women were randomised to the midwives unit and 944 to the labour ward.\n Maternal and perinatal morbidity.\n Of the women randomised to the midwives unit, 647 (34%) were transferred to the labour ward antepartum, 303 (16%) were transferred intrapartum, and 80 (4%) were lost to follow up. 870 women (46%) were delivered in the midwives unit. Primigravid women (255/596, 43%) were significantly more likely to be transferred intrapartum than multi-gravid women (48/577, 8%). Significant differences between the midwives unit and labour ward were found in monitoring, fetal distress, analgesia, mobility, and use of episiotomy. There were no significant differences in mode of delivery or fetal outcome.\n Midwife managed intrapartum care for low risk women results in more mobility and less intervention with no increase in neonatal morbidity. However, the high rate of transfer shows that antenatal criteria are unable to determine who will remain at low risk throughout pregnancy and labour.", "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.", "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.", "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.", "Genital tract trauma after spontaneous vaginal childbirth is common, and evidence-based prevention measures have not been identified beyond minimizing the use of episiotomy. This study randomized 1211 healthy women in midwifery care at the University of New Mexico teaching hospital to 1 of 3 care measures late in the second stage of labor: 1) warm compresses to the perineal area, 2) massage with lubricant, or 3) no touching of the perineum until crowning of the infant's head. The purpose was to assess whether any of these measures was associated with lower levels of obstetric trauma. After each birth, the clinical midwife recorded demographic, clinical care, and outcome data, including the location and extent of any genital tract trauma. The frequency distribution of genital tract trauma was equal in all three groups. Individual women and their clinicians should decide whether to use these techniques on the basis of maternal comfort and other considerations.", "We assessed the effectiveness of the home-visiting system in reducing the care provided in maternity units, especially hospitalization, and attempted to establish whether this system increases women's satisfaction with medical care. The trial involved 158 women and was conducted in four maternity units in Paris. A policy of one or two weekly visits by domiciliary midwives was compared with the usual policy of the hospitals. The study was restricted to women with moderate threatened preterm labor between 26 and 36 weeks of gestation. No decrease in the number of women hospitalized or the number of days spent in hospital was observed in the intervention group, but the number of prenatal visits to outpatient clinics was significantly smaller in the intervention than control group. Satisfaction with medical care during the episode of threatened preterm labor was much greater in the intervention group. Home visits by a midwife were considered by the women to be a better care system than numerous outpatient visits or hospitalization. Our results for medical care suggest that the introduction of the home-visiting system did not greatly alter medical practice in the maternity units, although this system had been designed to avoid or reduce hospitalization." ]

[ "7835254", "7974045", "3285637" ]

[ "Factors affecting the morbidity of vitamin D deficiency rickets and primary protection.", "Rickets in very-low-birth-weight infants born at Baragwanath Hospital.", "Double blind study on the need for vitamin D supplementation in prepubertal children." ]

[ "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.", "Disturbed mineral and bone metabolism has been reported to occur frequently in very-low-birth-weight infants fed breast-milk during the first 3 months of life. This study was designed to assess the prevalence of disturbed mineral homeostasis in a breast-milk-fed very-low-birth-weight population at Baragwanath Hospital and to determine whether the addition of a preterm infant formula to the feeds would reduce this prevalence and increase the rate of weight gain. Fifty-three neonates weighing less than 1 200 g at birth were monitored for weight gain, growth and biochemical and radiological evidence of metabolic bone disease at 2-weekly intervals during hospitalisation and for 18 weeks after discharge. The infants were randomised at 2 weeks of age to receive either breast-milk only, or a combination of breast-milk and a premature formula containing 550 mg calcium and 300 mg phosphorus. All infants received 800 IU vitamin D daily from day 14. Weight gain and growth were similar in both groups. Calcium and phosphorus intakes were higher in the mixed feeding group, but did not affect serum mineral levels. Radiological rickets was uncommon in both groups although periosteal reactions and osteopenia occurred frequently and with similar prevalences. Vitamin D deficiency was not found to be a problem. In conclusion, overt rickets is not a major problem in very-low-birth-weight infants born at Baragwanath Hospital, although biochemical abnormalities occur frequently.(ABSTRACT TRUNCATED AT 250 WORDS)", "Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown." ]

[ "9432077", "9738752", "3124628", "3172958", "3324594", "7282909", "11773839", "14758376", "3553455", "8509691" ]

[ "Use of antibiotic prophylaxis in ear surgery.", "Prophylactic antibiotics in surgery for chronic ear disease.", "The role of prophylactic antibiotics in middle ear surgery. A study on phenoxymethylpenicillin prophylaxis.", "Antimicrobial prophylaxis in ear surgery.", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial.", "Effectiveness of prophylactic antibiotic treatment in mastoid surgery.", "Preoperative topical ofloxacin solution for tympanoplasty: a randomized, controlled study.", "Prophylactic ciprofloxacin drops after tympanostomy tube insertion.", "Perioperative antibiotic prophylaxis for prevention of postoperative neurosurgical infections. A randomized clinical trial.", "The use of antibiotic/steroid ear drops to reduce post-operative otorrhoea and blockage of ventilation tubes. A prospective study." ]

[ "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.", "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.", "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.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases.", "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.", "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.", "To evaluate the effectiveness of prophylactic ciprofloxacin drops in decreasing the incidence of post-tympanostomy otorrhea, and the relation between middle ear content and post-tympanostomy otorrhea.\n One hundred and fifty patients aged 3-14 years underwent tympanostomy and tube insertion at the Prince Rashid Ben Al-Hasan Hospital, Al-Husn, Jordan during the interval between February 2000 to January 2003. The patients were randomized into 3 groups: group 1 (control group) received no antibiotic drops, group 2 received a single dose of ciprofloxacin drops intraoperatively and group 3 received an intraoperative dose followed by 5-day postoperative course.\n Application of topical ciprofloxacin after tympanostomy tube insertion was associated with a significantly lower incidence of early post-tympanostomy otorrhea. The rate of otorrhea for the control group was 16.5% and the treatment groups were (group 1) 8.4%, (group 2) 8.2% and p=0.011. A single dose of antibiotics was effective when patient's middle ears were dry or had serous effusions. For those whose ears had mucoid or purulent content a 5-day course was indicated.\n Topical administration of a single dose of ototopical ciprofloxacin after surgery is an effective treatment for the prevention of early post-tympanostomy otorrhea, and a prolonged course (5 days) may be indicated for those whose ears had purulent or thick mucoid contents, and the content of middle ear are important in predicating postoperative otorrhea.", "The authors report the results of a randomized, prospective study to assess the effectiveness of perioperative antibiotic prophylaxis in preventing postoperative infections following clean neurosurgical operations. The study group comprised 846 patients treated between October, 1979, and June, 1984. Antibiotics, including cefazolin and gentamicin, were administered only in the immediate preoperative and intraoperative periods. Sixteen patients, none of whom developed infections, were excluded from final statistical analysis because they had inadvertently been entered into the study while failing to meet entry criteria. Fifteen wound infections (3.64%) developed in the group of 412 patients who did not receive antibiotics, whereas only four infections (0.96%) were identified among the 418 patients who received antibiotics. The difference is statistically significant (p = 0.008) and represents a 74% reduction in infection rate with antibiotics. An analysis of subgroups of surgical procedures revealed a dramatic decrease in craniotomy infections from 6.77% to 0% (p = 0.003). Of the four infections that occurred among the antibiotic-treated patients, three were in cases where foreign bodies had been implanted. No complications of antibiotic usage were identified. The rates of infection in areas of the body other than the surgical wound were no different in the antibiotic-treated and nontreated groups. All wound infections in both antibiotic-treated and nontreated patients involved similar types of Gram-positive organisms, suggesting that antibiotic prophylaxis did not produce infections with resistant or unusual organisms. This study, combined with other recently published analyses, suggests that routine perioperative antibiotic prophylaxis can significantly reduce the incidence of postoperative neurosurgical infections.", "This prospective randomized study investigates whether the use of antibiotic/steroid ear drops (Betnesol-N) is effective in reducing early post-operative otorrhoea and blockage of ventilation tubes (VTs). The study included 162 children who had bilateral VT insertion and used Betnesol-N ear drops in one ear only for three days after surgery, the other ear was left as control. These children were reviewed two weeks later and their ears were examined for VT patency, presence of blood or of mucopus. Statistical analysis of our results showed that the use of Betnesol-N ear drops has significantly reduced the incidence of post-operative otorrhoea within two weeks of VTs insertion (p < 0.01). However, these drops did not have a significant effect on the blockage rates of VTs with dried blood (p > 0.05)." ]

[ "17954514", "17954515", "14512476" ]

[ "Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine.", "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." ]

[ "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].", "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." ]

[ "10596681", "9337824", "8765628", "9192929" ]

[ "A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients.", "Effect of long-term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia.", "Inhaled nitric oxide in term infants with hypoxemic respiratory failure.", "Training with supplemental oxygen in patients with COPD and hypoxaemia at peak exercise." ]

[ "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.", "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.", "To determine whether inhaled nitric oxide (NO) administered during conventional mechanical ventilation could produce improvements in oxygenation and reduce the incidence of meeting extracorporeal membrane oxygenation (ECMO) criteria in infants with hypoxemia.\n Prospective, randomized, controlled trial. Enrolled infants were assigned to conventional treatment with or without adjunctive inhaled NO. Control infants meeting failure criteria (partial pressure of arterial oxygen (PaO2)<80 mm Hg (10.7 kPa)) were allowed to cross over. Caregivers were not masked to group assignment.\n Neonatal intensive care units at the University of Alabama Hospital and the Children's Hospital of Alabama, October 1993 to May 1994.\n Newborn infants, both term and near-term, with PaO2 less than 100 mm Hg (13.3 kPa) who were receiving mechanical ventilation with 100% oxygen. Exclusion criteria included major congenital anomalies, diaphragmatic hernia, profound asphyxia, and significant bleeding.\n Inhaled NO was initiated in the NO group at a dose of 20 to 40 ppm and advanced stepwise to 80 ppm if PaO2 remained less than 100 mm Hg (13.3 kPa).\n Primary outcome variables were treatment failure and meeting of ECMO criteria before crossover. Improvement in oxygenation and ultimate use of ECMO or high-frequency oscillatory ventilation were secondary outcome variables.\n Seventeen neonates with hypoxemia were enrolled; 16 had echocardiographic evidence of pulmonary hypertension, and eight had extrapulmonary shunting. At 1 hour of treatment, two infants in the NO group responded with increases in PaO2 of more than 100 mm Hg (13.3 kPa); after crossover, two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) and one control infant had an increase in PaO2 of more than 10 mm Hg (1.3 kPa). All control infants met failure criteria and crossed over to receive NO; two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) with NO treatment. Despite initial responses, all subjects in both groups eventually met failure criteria. There were no differences between groups in primary outcome variables.\n Although inhaled NO produced a transient improvement in oxygenation in some infants, it did not reduce the incidence of meeting ECMO criteria in this population.", "Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD. A randomized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise (arterial oxygen saturation (Sa,O2) <90% at peak exercise). All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration. They were assigned either to general exercise training while breathing room air (GET/RA group: forced expiratory volume in one second (FEV1) 38% of predicted; arterial oxygen tension (Pa,O2) 10.5 kPa at rest; Pa,O2 7.3 kPa at peak exercise), or to GET while breathing supplemental oxygen (GET/O2 group: FEV1 29% pred; Pa,O2 10.2 kPa at rest; Pa,O2 7.2 kPa at peak exercise). Sa,O2 was not allowed to fall below 90% during the training. The effects on exercise performance while breathing air and oxygen, and on quality of life were compared. Maximum workload (Wmax) significantly increased in the GET/RA group (mean (SD) 17 (15) W, p<0.01), but not in the GET/O2 group (7 (25) W). Six minute walking distance (6MWD), stair-climbing, weight-lifting exercise (all while breathing room air) and quality of life significantly increased in both groups. Acute administration of oxygen improved exercise performance before and after training. Training significantly increased Wmax, peak carbon dioxide production (V'CO2) and 6MWD while breathing oxygen in both groups. Differences between groups were not significant. Pulmonary rehabilitation improved exercise performance and quality of life in both groups. Supplementation of oxygen during the training did not add to the effects of training on room air." ]

[ "2792672", "2194894", "16259890", "10733802", "16670131", "11466598" ]

[ "A double-blind, randomized, sham-controlled trial of the gastric bubble for obesity.", "Intragastric balloon in the treatment of super-morbid obesity. Double-blind, sham-controlled, crossover evaluation of 500-milliliter balloon.", "Laparoscopic adjustable gastric banding versus open vertical banded gastroplasty: a prospective randomized trial.", "Surgery for Obesity- An Update of a Randomized Trial.", "Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial.", "Conceptualisation and evaluation of a cognitive-behavioural training programme for children and adolescents with obesity." ]

[ "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.", "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.", "Laparoscopic adjustable gastric banding (LAGB) and open vertical banded gastroplasty (VBG) are treatment modalities for morbid obesity. However, few prospective randomized clinical trials (RCT) have been performed to compare both operations.\n 100 patients (50 per group) were included in the study. Postoperative outcomes included hospital length of stay (LOS), complications, percent excess weight loss (%EWL), BMI and reduction in total comorbidities. Follow-up in all patients was 2 years.\n LOS was significantly shorter in the LAGB group. 3 LAGB were converted to open (1 to gastric bypass). Directly after VBG, 3 patients needed relaparotomies due to leakage, of which one (2%) died. After 2 years, 100% follow-up was achieved. BMI and %EWL were significantly decreased in both groups but significantly more in the VBG group compared to the LAGB group (31.0 kg/m2 and 70.1% vs 34.6 and 54.9% respectively). Co-morbidities significantly decreased in both groups in time. 2 years after LAGB, 20 patients needed reoperation for pouch dilation/slippage (n=12), band leakage (n=2), band erosion (n=2) and access-port problems (n=4). In the VBG group, 18 patients needed revisional surgery due to staple-line disruption (n=15), narrow outlet (n=2) or insufficient weight loss (n=1). Furthermore, 8 VBG patients developed an incisional hernia.\n This RCT demonstrates that, despite the initial better weight loss in the VBG group, based on complication rates and clinical outcome, LAGB is preferred. It had a shorter LOS and less postoperative morbidity.", "BACKGROUND: A prospective, randomized trial comparing vertical banded gastroplasty (VBG) and gastric bypass (GB) was performed on 106 patients between 1987 and 1990. METHODS AND RESULTS: Failures of these two operations (manifested by failure to lose weight, late weight gain or intolerance of adequate oral intake) were treated by means of a third operation, isolated gastric bypass (IGB), in which the small gastric pouch was isolated from the gastric fundus. The latter operation was significantly better than VBG or GB and achieved a 63% success rate, i.e. body mass index (BMI) < 35 kg m(2) and less than 50% excess weight. During the year following this trial an additional 54 patients underwent IGB. When this operation was performed for morbid obesity and was the Initial procedure, 96% of the patients achieved a successful result. If IGB was performed as a revision procedure or for super obesity (BMI > 50 kg m(2)), the success rate was 63% with 100% follow-up at 40 months. Major morbidity occurred in six of the 160 patients who underwent 195 operations (the trial period and subsequent year). There were no deaths and follow-up was 98%. CONCLUSIONS: The ideal gastric operation based on this study emphasizes the following requirements: a small pouch (< 15 ml) totally separated from the stomach, a pouch not dependent on staples, placed in the dependent position to prevent stasis, constructed without foreign material and with an anastomosis which permits ingestion of solid food.", "Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this.\n To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy.\n Randomized, controlled trial.\n University departments of medicine and surgery and an affiliated private hospital.\n 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community. Interventions: Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group).\n Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years.\n At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores).\n The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months.\n Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program.", "Obesity is common in children and adolescents with incidence rates increasing both nationally and internationally. Its causes are complex and multifaceted, and obesity is associated with high morbidity and mortality as well as psychological distress. Multidimensional programmes are necessary in the treatment of this chronic disease in order to change eating and physical activity habits. A cognitive-behavioural training programme was developed and evaluated. In combination with diet and exercise, this special group programme that includes well established behavioural methods, was expected to result in long-term weight reduction and decrease of psychological distress in connection with obesity.\n As part of the six week in-patient rehabilitation for children and adolescents at Viktoriastift in Bad Kreuznach, the three-part programme (experimental group, EG) was compared with a programme that differed only in the psychological intervention component (instead of the specific training programme they undertook muscle relaxation training, comparison group, CG).\n In total, 197 children and adolescents between 9 and 19 y-of-age were recruited into the study.\n Somatic (eg weight status), behavioural (eg eating behaviour) and psychological (eg quality of life) outcomes were assessed at five points in time: two weeks before the intervention, at the beginning and end of the programme, as well as six months and one year post-intervention. The study started in spring 1997. Main outcomes will be presented.\n Pre- vs post-intervention-tests showed significant improvements in self-reported eating behaviours for the EG compared with the CG (F=6.38, P<0.05); these changes were independent of age and sex. The weight status measured as the percentage of overweight dependent on height was reduced in both groups immediately after the intervention and at follow-up (F=16.51, P<0.01). Reduction in the prevalence of obesity tended to be higher in the EG than in the CG (15% vs 10%). Self-reported quality of life increased from before the intervention to follow-up more in the EG than in the CG (F=3.27, P=0.08). In all, the acceptance of the behavioural patient education programme was good.\n In summary, evaluation results indicate that the cognitive-behavioural training programme is a promising approach to alter obesity-related habits and to reduce somatic and psychosocial consequences. Long-term effects after two years are expected to underscore these results." ]

[ "2406126", "16468111", "4006888", "2044499" ]

[ "Randomized trial of a program to enhance the competencies of children with epilepsy.", "[Education of children with epilepsy and their parents by the modular education program epilepsy for families (FAMOSES)--results of an evaluation study].", "Effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures.", "Impact of the Children's Epilepsy Program on parents." ]

[ "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.", "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 group of 18 children with refractory epileptic seizures was divided into three groups--behavior modification treatment, attention control, and control groups--with the purpose of investigating the effects of a learning-based broad-spectrum treatment program superimposed on a regular medical treatment program. The design consisted of a 10-week baseline, 6-week intervention, and 10-week and 1-year follow-ups. A combination of number of seizures and seizure duration--termed \"seizure index\"--was used as a dependent measure. There was a significant reduction in seizure index only for those children receiving the behavior modification treatment, at both follow-ups. The results indicate that this behavioral treatment program may be of substantial help to children with epilepsy who are resistant to conventional drug therapy.", "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)." ]

[ "18607963", "15072419" ]

[ "Intratympanic gentamicin therapy for control of vertigo in unilateral Menire's disease: a prospective, double-blind, randomized, placebo-controlled trial.", "Selective vestibular ablation by intratympanic gentamicin in patients with unilateral active Ménière's disease: a prospective, double-blind, placebo-controlled, randomized clinical trial." ]

[ "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.", "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." ]

[ "18383539", "19066176", "19644849", "9920948" ]

[ "Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study.", "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.", "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.", "A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate." ]

[ "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.", "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.", "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.", "Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate.\n In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks.\n The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P<0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept.\n In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone." ]

[ "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." ]

[ "17462166", "19758364", "15482502", "16740868", "15832550", "17700083", "11473908", "16271570", "17076751" ]

[ "Additional therapy for young children with spastic cerebral palsy: a randomised controlled trial.", "Intensive speech and language therapy for older children with cerebral palsy: a systems approach.", "A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.", "Quality of reporting of randomized, controlled trials in cerebral palsy.", "Effects of constraint-induced movement therapy in young children with hemiplegic cerebral palsy: an adapted model.", "A randomized, controlled trial of a home-based intervention program for children with autism and developmental delay.", "Multicentre controlled trial of parenting groups for childhood antisocial behaviour in clinical practice.", "Efficacy of forced-use therapy in hemiplegic cerebral palsy.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change." ]

[ "To investigate whether, in the short and medium term, additional support by (a) a physiotherapy assistant improved physical function in young children with spastic cerebral palsy and (b) a family support worker improved family functioning.\n This was a multi-centre randomised controlled trial (RCT) with blinded assessments and a cost-effectiveness analysis. The children studied had spastic cerebral palsy that was the consequence of perinatal adversity. All were less than 4 years old on entry to the study.\n In the child development centre and in the home.\n Seventy-six families completed the intervention period. Forty-three families were reassessed 6 months after the end of the intervention and 34 of these after a further 6-month period.\n Randomisation was to: (a) a group who received extra physiotherapy from a physiotherapy assistant; (b) a group who received standard physiotherapy; and (c) a group where the child received standard physiotherapy and the family was also visited by a family support worker. Children in all groups continued to receive standard physiotherapy in addition to the study interventions.\n The child outcome measures were motor functioning, developmental status and adaptive functioning. The family outcome measures were self-reported maternal stress, level of family needs and parental satisfaction.\n There was no evidence that additional physical therapy for 1 hour per week for 6 months by a physiotherapy assistant improved any child outcome measure in the short or medium term. Intervention by a family support worker did not have a clinically significant effect on parental stress or family needs. Over the 6-month period the total cost of services for each child ranged from 250 pounds to 6750 pounds, with higher costs associated with children with more severe impairments. No significant relationship was found between measures of intensity of services received by the children and families and the main outcome measures. Low-functioning children, in terms of both motor and cognitive function, were more likely to receive more services in terms of range and frequency. Parents generally reported high satisfaction ratings after all interventions and some stated that the interventions had benefited the child and/or the family. There was therefore a discrepancy between the perceptions of these parents and the objective, quantitative measurements. The family support workers identified a small number of families who were experiencing considerable family problems, but who had not been referred for appropriate support by any other agency.\n The findings of this study provide support for the current literature that there was no evidence that additional intervention (in this case by a physiotherapy assistant or family support worker) helped the motor or general development of young children with spastic cerebral palsy. Nor was there any quantitative evidence that providing extra family support helped levels of parental stress and family needs. The implication was that the provision of extra physical therapy does not necessarily improve the motor function of a young child with cerebral palsy and additional family support should not automatically be assumed to be beneficial. In addition, no significant association was found between the intensity of the local services provided and any outcome measure, other than a slight association with lowered family needs. The provision of local services was related to the severity of the child's impairments and not to family difficulties. A small group of families with complex family problems needed more service input. There was a wide range in the costs of services. Research is needed to examine what 'sufficient' levels of provision or therapy might be for which children and which families. A time series of different levels of input and outcomes would provide valuable information for practitioners. It is also recommended that future assessments of therapies of this type adopt a similar multifaceted approach, which is likely to be more suitable than a simple RCT for the evaluation of clinical interventions where the effects are complex. The most appropriate measures of outcome should be used, including assessment of provision of information and emotional support for families.", "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.", "Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone.\n The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments.\n All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain.\n A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.", "In conducting reviews on the effectiveness of physiotherapy interventions on children with cerebral palsy, the assessment of trials can be hampered by problems in reporting. Therefore, we set out to evaluate trial reporting by using the Consolidated Standards of Reporting Trials (CONSORT) statement recommendations.\n Randomized, controlled trials published in 1990 or later were identified in literature searches for reviews on the effectiveness of physiotherapy interventions on children with cerebral palsy. Two independent reviewers evaluated the trial reporting by using a modified 33-item Consolidated Standards of Reporting Trials checklist.\n We identified 15 randomized, controlled trials. Almost half (48%) of the applicable items were reported adequately. Inadequate reporting was found in the following items: outcome measures, sample-size determination, details of the sequence generation, allocation concealment and implementation of the randomization, success of assessor blinding, recruitment and follow-up dates, intention-to-treat analysis, precision of the effect size, co-interventions, and adverse events.\n Only a small number of sufficiently reported trials were found. Because nearly all items had been described in at least 1 article, high-quality reporting seems feasible. Assessment of trials depends on appropriate reporting, and poor reporting jeopardizes judgments on the clinical implications. Authors of randomized, controlled trials are encouraged to follow the Consolidated Standards of Reporting Trials criteria. There is a clear need to improve the quality of reporting of trials in this field.", "The aim of this study was to evaluate the effects of a modified version of constraint-induced (CI) movement therapy on bimanual hand-use in children with hemiplegic cerebral palsy (CP; age range 18 mo to 4 y) and to make a comparison with conventional paediatric treatment. Twenty-one children (13 females, eight males) completed the CI therapy programme and 20 children (12 males, eight females) served as a control group. Children in the CI therapy group were expected to wear a restraint glove for 2 hours each day over a period of 2 months. The training was based on principles of motor learning used in play and in motivational settings. To evaluate the effect of treatment, the Assisting Hand Assessment (AHA) was used. Assessments took place on three occasions: at onset, after 2 months, and 6 months after the first assessment. A significant interaction was found between group and AHA measure (ANOVA, F(2,74) = 5.64, p = 0.005). The children who received CI therapy improved their ability to use their hemiplegic hand significantly more than the children in the control group after 2 months, i.e. after treatment. Effect size was high after treatment and remained medium at 6 months. As the treatment was tailored to each child's capacity and interests, little frustration was experienced by the children.", "This study aimed to (1) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and (2) describe the characteristics of children and families who benefit most from the intervention.\n Fifty-nine children, aged 3-5 years, with no cerebral palsy, participated in the study. Half of the group was randomized to receive an additional program in their homes. A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns. All children were assessed before and after the intervention, and families completed questionnaires assessing family stress, support, and empowerment on both occasions. Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance.\n Change in cognitive development and behavior (in the centers) over time favored the children who received the extra intervention (p = .007 and p = .007, respectively). The groups did not differ on any of the family measures of change. Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families.\n Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families, especially those with few resources and relatively high stress.", "To see whether a behaviourally based group parenting programme, delivered in regular clinical practice, is an effective treatment for antisocial behaviour in children.\n Controlled trial with permuted block design with allocation by date of referral.\n Four local child and adolescent mental health services.\n 141 children aged 3-8 years referred with antisocial behaviour and allocated to parenting groups (90) or waiting list control (51).\n Webster-Stratton basic videotape programme administered to parents of six to eight children over 13-16 weeks. This programme emphasises engagement with parental emotions, rehearsal of behavioural strategies, and parental understanding of its scientific rationale.\n Semistructured parent interview and questionnaires about antisocial behaviour in children administered 5-7 months after entering trial; direct observation of parent-child interaction.\n Referred children were highly antisocial (above the 97th centile on interview measure). Children in the intervention group showed a large reduction in antisocial behaviour; those in the waiting list group did not change (effect size between groups 1.06 SD (95% confidence interval 0.71 to 1.41), P<0.001). Parents in the intervention group increased the proportion of praise to ineffective commands they gave their children threefold, while control parents reduced it by a third (effect size between groups 0.76 (0.16 to 1.36), P=0.018). If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16%.\n Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions. Follow up is needed to see if the children's poor prognosis is improved and criminality prevented.", "To determine the efficacy of forced-use therapy (FUT) on the improvement of upper-extremity function in children with hemiplegic cerebral palsy (CP).\n Prospective case series.\n Outpatient ambulatory clinic in South Korea.\n Thirty-one patients with hemiplegic CP were assigned to the FUT group (n=18) or to the control group (n=13). The mean age of the patients in the FUT group was 33.2 months and in the control group it was 43.2 months.\n The FUT group wore a short-arm Scotchcast on the unaffected arm for 6 weeks and also participated in a conventional rehabilitation program that included stretching exercises and functional occupational therapy for the upper extremity. The control group underwent the conventional rehabilitation program only.\n Hand function tests, including the box and block test (BBT), Erhardt Developmental Prehension Assessment (EDPA), and WeeFIM instrument taken before and after 6 weeks of treatment.\n Before treatment, there was no significant difference between groups in the BBT, EDPA, and WeeFIM scores. After 6 weeks of treatment, however, the FUT group showed significant improvement in the affected arm in the BBT and EDPA scores, compared with the control group (P<.05). The self-care score on the WeeFIM was also significantly improved in the FUT group (P<.05).\n FUT combined with a conventional rehabilitation program appears to be more effective than a rehabilitation program alone in improving affected hand function in children with hemiplegic CP.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families." ]

[ "10213547", "6791596", "413493", "11379805", "7573849", "3133964", "3929698", "8387933", "2167369", "6418561", "10582197", "1615179", "8265272", "6230059", "2105675", "8087189", "7930301", "7638372", "3092689" ]

[ "Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1-4-year-old children with moderate asthma.", "Nebulised cromoglycate, theophylline, and placebo in preschool asthmatic children.", "Nebulized sodium cromoglycate in young asthmatic children. Double-blind trial.", "Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice.", "A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma.", "Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma.", "Nebulised sodium cromoglycate in recurrently wheezy preschool children.", "Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children.", "Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate.", "Pretreatment of exercise-induced asthma in children using disodium cromoglycate and fenoterol inhalation powder.", "Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma.", "Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up.", "Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children.", "Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life.", "Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma.", "Inhibition of exercise-induced-asthma (EIA) by nedocromil sodium and sodium cromoglycate in children.", "Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.", "Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study).", "Nebulised sodium cromoglycate in the treatment of wheezy bronchitis. A multicentre double-blind placebo controlled study." ]

[ "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.", "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.", "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.", "Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma.\n To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial.\n Health economics were evaluated in 138 children, ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months; budesonide 400 microg/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment.\n In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195; US $487; Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication.\n A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate.", "We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.", "Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate, reproterol, sodium cromoglycate plus reproterol, and placebo in exercise-induced asthma. Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited exercise-induced asthma. The best protection is effected by the combination of sodium cromoglycate and reproterol. A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive.", "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.", "To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG) administered by metered dose inhaler (MDI) in preventing exercise-induced asthma (EIA), 12 asthmatic children with EIA were studied in a randomized, double-blind, cross-over, placebo-controlled study. NS and SCG were given by MDI alone, and by MDI with a 700 ml spacer device (Fisonair, Fisons, UK), in order to assess the benefit of using such a device. Following a baseline exercise challenge, the protective effect of NS, SCG or placebo was evaluated in each subject. The percentage fall in forced expiratory volume in one second, and percentage protection were measured. NS and SCG provided a significant and comparable protection from EIA, and both were better than placebo. No further improvement was observed after drug administration via the spacer. Both NS and SCG are effective in preventing EIA in children, when administered at the recommended clinical dose, and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good.", "A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals.", "The effect of pretreatment with inhalation powder containing fenoterol, sodium cromoglycate, fenoterol plus sodium cromoglycate and placebo, in the prevention of exercise-induced asthma was compared in a randomized, double-blind, cross-over investigation including 17 asthmatic children with exercise-induced asthma. Six minutes of treadmill running was carried out in a climate chamber 30 minutes after pretreatment on the four test days. The post-exercise fall in PEF after pretreatment with fenoterol was 7%, with sodium cromoglycate 20%, with fenoterol plus sodium cromoglycate 6% and after placebo 27%. Both sodium cromoglycate and fenoterol provided protection against exercise-induced asthma (p less than 0.05 and p less than 0.001). Fenoterol gave significantly better protection than sodium cromoglycate (p less than 0.001), and it is concluded that the treatment of choice for the prevention of exercise-induced asthma is the inhalation of a beta 2-agonist.", "According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed.", "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.", "To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.", "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.", "A double-blind trial involving 20 asthmatic patients was carried out to test the effect of fenoterol and sodium cromoglycate alone and in combination on ventilatory function one hour after medication. The results show that fenoterol, whether alone or in combination with sodium cromoglycate, can increase the forced expiratory volume in one second (FEV1) by up to 25% both after rest and after exercise. No patient suffered a decrease in FEV1 using fenoterol, and at least 80% of them recorded an increase in ventilatory ability. Sodium cromoglycate was of no benefit in eliminating early reaction to exercise-induced asthma.", "Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma.", "Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.", "Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy.", "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." ]

[ "2267922", "7359263", "3089439", "2188543", "9802368", "7638372" ]

[ "Placebo controlled trial of systemic corticosteroids in acute childhood asthma.", "Corticosteroids in status asthmaticus.", "Short course of steroids in home treatment of children with acute asthma.", "Early administration of corticosteroids in emergency room treatment of acute asthma.", "Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone.", "Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study)." ]

[ "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.", "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.", "A double blind, randomised, placebo controlled study of the treatment of children with acute asthma at home showed that a three day course of prednisolone hastened improvement of both asthmatic symptoms and peak expiratory flow rates. Thus all asthmatic children who present with an acute attack should be considered for treatment with corticosteroids in addition to bronchodilators not only to prevent possible deterioration but also to speed recovery.", "To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma.\n Randomized, double-blind, placebo-controlled trial.\n The emergency room of a large, urban hospital with primary and referral care responsibilities.\n Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups.\n The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours.\n Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group.\n These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted.", "Inhaled corticosteroids have a greater antiinflammatory potency and fewer systemic effects than intravenous, intramuscular, or oral corticosteroids. However, their role in acute asthma has not been established. We prospectively investigated the efficacy and safety of inhaled corticosteroids in controlling moderately severe acute asthma attacks in children who were treated in the emergency department.\n Children who were treated in the emergency department with moderately severe asthma attacks after receiving treatment with inhaled terbutaline were allocated by double-blind design to receive 1 dose of either 1600 micro(g) budesonide turbohaler or 2 mg/kg prednisolone. The pulmonary index score and peak expiratory flow rate were measured hourly for the first 4 hours. After discharge the children were treated with the same initial doses given 4 times daily, followed by a 25% reduction in dose every second day for 1 week. Parents recorded asthma symptoms and use of beta-2 agonists on a daily diary card. Serum cortisol concentration was measured at the end of weeks 1 and 3.\n Twenty-two children (11 in each group) with similar baseline parameters completed the study. There was a similar improvement in pulmonary index score and peak expiratory flow rate in the 2 groups. Children treated with budesonide showed an earlier clinical response than those given prednisolone, who also showed a decrease in serum cortisol concentration.\n In children with moderately severe asthma attacks who were treated in the emergency department, a short-term dose schedule of inhaled budesonide turbohaler, starting with a high dose and followed by a decrease over 1 week, is at least as effective as oral prednisolone, without suppressing serum cortisol concentration.", "Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy." ]

[ "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." ]

[ "15479682", "9354192", "21453880", "18240282" ]

[ "Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine.", "Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis.", "A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis.", "Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells." ]

[ "Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis.\n In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses.\n The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different.\n The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.", "Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non-pathogenic E. coli.\n A total of 120 patients with inactive ulcerative colitis were included in a double-blind, double-dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse-free times and global assessment.\n The start and end scores of the CAI demonstrated no significant difference (P = 0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse-free time of 103 +/- 4 days for mesalazine and 106 +/- 5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported.\n From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.", "To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis.\n Patients with left-sided ulcerative colitis in remission - including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients.\n Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p=0.37). The median time to relapse was 125.5days (range 11-391 days) in the probiotic group and 104 days (range 28-369 days) in the placebo group respectively, (p=0.683). Probio-Tec AB-25 was overall well tolerated.\n In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).\n Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.", "Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown.\n We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-beta [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1beta and Foxp3 mRNA expression was also evaluated.\n During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25(high) and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1beta mRNA expression, and a significant increase in Foxp3 mRNA expression.\n We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells." ]

[ "10819344", "9821420" ]

[ "Five vs. ten days of antibiotic therapy for acute otitis media in young children.", "A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children." ]

[ "Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.\n In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.\n Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).\n The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.", "All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.\n In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.\n Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).\n When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM." ]

[ "786665", "15741443", "2403903" ]

[ "A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis.", "Inhaled fluticasone in bronchiectasis: a 12 month study.", "The National Mucolytic Study. Results of a randomized, double-blind, placebo-controlled study of iodinated glycerol in chronic obstructive bronchitis." ]

[ "In 69 out-patients with chronic bronchitis in 6 centres the effects of acetylcysteine 600 mg daily, 3 days a week for 6 months, and a placebo have been compared in a double-blind controlled trial. Thirty-five patients were treated with the mucolytic and 34 with the dummy preparation. In the former the clinical course of the chronic bronchitis improved to a greater extent and a significantly lower number of exacerbations was observed. The advantages of long-term oral treatment with the mucolytic in chronic bronchitis suggest that it may be useful as an alternative to long-term antibiotic prophylaxis, or to complement brief courses of antibiotics, in addition to the usual physiotherapy.", "The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation.\n After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion.\n 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency </=2/year (p = 0.04), and sputum purulence score >5 (p = 0.03).\n ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.", "Seventy-four pulmonologists and one allergist were recruited to assess the efficacy and safety of iodinated glycerol (Organidin), 60 mg qid, vs placebo in patients with stable chronic obstructive bronchitis in a randomized, double-blind, placebo-controlled, parallel design. A total of 361 patients (180 to iodinated glycerol and 181 to placebo) who complained of cough and difficulty bringing up sputum entered the eight-week study. Evaluations were based upon eight primary symptom efficacy parameters (cough frequency, cough severity, chest discomfort, dyspnea, ease in bringing up sputum, patient and physician global assessments, and a derived patients' global assessment), and six secondary parameters (frequency of aerosol bronchodilator use, incidence and duration of acute exacerbations, frequency of concomitant medication use, incidences of adverse experiences and dropouts). Cough frequency, cough severity, chest discomfort, patients' ease in bringing up sputum, patients' overall condition, and a derived subject global assessment were significantly (p less than 0.05) improved by iodinated glycerol as compared with placebo within eight weeks of treatment. Dyspnea showed a trend toward improvement and the physicians' global evaluation showed no significant difference between groups. Similar findings were noted in a subgroup analysis of moderately-to-severely affected patients. The mean duration (days) of acute exacerbations and number of dropouts attributable to adverse experiences were significantly less (p less than 0.05) in the iodinated glycerol group.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "15479896", "1985618", "11678298", "9855212", "3890159" ]

[ "Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double blind, placebo controlled trial.", "Corticosteroid injections in adhesive capsulitis: investigation of their value and site.", "Comparison of the efficacy of local corticosteroid injection and physical therapy for the treatment of adhesive capsulitis.", "Treatment of \"frozen shoulder\" with distension and glucorticoid compared with glucorticoid alone. A randomised controlled trial.", "A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis." ]

[ "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.", "Forty-eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals. The treatment groups were (1) intra-articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine. The same physical therapy program was carried out for all patients. Assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy. There was no significant difference in outcome between intrabursal injection and intra-articular injection. Injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion, but partial, transient pain relief occurred in two thirds of the steroid-treated patients.", "Adhesive capsulitis is a common musculoskeletal disorder mainly affecting middle aged adults. It is associated with generalized pain and tenderness in the shoulder joint with severe loss of active and passive ranges of motion in all planes. The aim of this study was to compare the efficacy of local steroid injection and physical therapy measures for treating this disorder. Ten male and 10 female patients were enrolled in the study. The patients were divided randomly into two groups and treated with either 40 mg methylprednisolone acetate injection with local anesthetic (group A) or physical therapy measures plus nonsteroidal anti-inflammatory drugs (group B). The mean ages of the patients were 55.6+/-12.2 years in group A and 56.4+/-7.1 years in group B. Clinical assessment was performed on initial visit and at the 2nd and 12th weeks. Active and passive range of motion was recorded and the visual analogue scale was used to evaluate pain intensity. At initial visit, these data in both groups of patients were not statistically different. Although both treatment regimens resulted in significant improvement in range of motion, the differences between mean external rotation at the 2nd and 12th weeks were not statistically significant in either group. The improvement in range of motion at the end of the study was similar in both groups (P>0.05). All patients reported improvement during the study. The differences between mean VAS scores at the 2nd and 12th weeks were statistically significant in both groups. In conclusion, local steroid injection therapy was found to be as effective as physical therapy for the treatment of adhesive capsulitis.", "This study is a comparison of treatments of idiopathic \"Frozen Shoulder\" (adhesive capsulitis), distension combined with steroid is compared with steroid alone. Evaluation was based on pain scales, analgesic usage, and range of motion outcome scales. Out of one-hundred twenty patients (age, mean 51, range 21-70) that were referred under the diagnosis FS, twenty-six fulfilled the criteria for inclusion in the study, but four patients did not want to participate in the trial, giving a total of 22 patients (age, mean 53, range 40-65) in the study. Patients were randomised by the envelope method. Two patients dropped-out, one in each treatment group thus leaving the study with 20 patients for the final statistical analysis. Eight were treated with steroid alone and 12 with distension combined with steroid. Patients received one treatment per week for a six weeks period with a follow-up at 12 weeks. They were evaluated by pain VAS on function and at rest within the study period, the different ranges of motion (ROM) were measured at inclusion time and subsequent afterwards at 3, 6, and 12 weeks. The VAS outcomes showed no difference between the treatments (VAS-function p=0,1; VAS-rest p=0.1), while in the distension group ROM showed significant improvement in all directions except extension (external p=0.0007, flexion p=0.03, extension p=0,01). The analgesic usage was significantly lower in the group treated with distension at the end of the study (p=0.008). A blinded clinical assessment of ROM also showed significant improvement (p=0.002). It is concluded that distension with steroid can seem to help in management of \"Frozen Shoulder\". Other studies seems to support the conclusion.", "In this report of a double-blind placebo-controlled trial of steroid injections for supraspinatus tendonitis, there was no statistical difference in the improvement in pain score between the two groups at 2 and 8 weeks of follow-up or in analgesic consumption. This trial casts further doubt on the efficacy of such treatment in soft tissue lesions around the shoulder." ]

[ "19948625", "19797985" ]

[ "Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.", "A placebo-controlled, fixed-dose study of aripiprazole in 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.", "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." ]

[ "16291160" ]

[ "A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis." ]

[ "Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.\n Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.\n Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.\n Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis." ]

[ "9143888" ]

[ "Indirect scatter laser photocoagulation to subfoveal choroidal neovascularization in age-related macular degeneration." ]

[ "Occult choroidal neovascularization (CNV), poorly defined on fluorescein angiography, is present in the majority of patients with exudative complications of age-related macular degeneration. For patients who present with this type of subfoveal CNV but who have useful visual acuity, no form of treatment is of proven benefit. Accordingly, a pilot randomized trial of indirect laser treatment was performed. The rationale of this treatment was to inhibit the CNV through laser-induced effects on the retinal pigment epithelium.\n Patients with occult subfoveal CNV without retinal pigment epithelial detachment and with visual acuity of 20/200 or better were randomized to treatment or control groups. A grid of laser burns was applied to the macula beyond the area of serous retinal detachment and of angiographically defined occult CNV.\n After an average follow-up of 38 months, there was no difference in mean final visual acuity (0.12 treated, 0.14 control) or clinical outcome between treated and untreated groups. Fluorescein angiography showed gradual enlargement in the occult CNV in 58% of eyes in both groups. A decrease in visual acuity to worse than 20/200 (54% of treated, 50% of control eyes) was associated with ingrowth of well-delineated CNV (6 treated, 7 control eyes) or progression to a fibroglial or atrophic scar (11 treated, 8 control eyes).\n No benefit was demonstrated for scatter photocoagulation of the macula in patients with age-related macular degeneration and occult subfoveal CNV with initially good visual acuity. There were, however, no complications related to treatment." ]

[ "11087881", "14530224" ]

[ "Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.", "Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial." ]

[ "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.", "Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform.\n To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis.\n Randomized, controlled trial.\n 600 office and clinical research sites.\n 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine.\n Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted.\n Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12.\n Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events.\n In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample." ]

[ "18853562", "16435703", "15530927", "18074710", "19171828", "15713204", "8907444", "20390477" ]

[ "Highlighting human form and motion information enhances the conspicuity of pedestrians at night.", "Limitations in drivers' ability to recognize pedestrians at night.", "High visibility safety apparel and nighttime conspicuity of pedestrians in work zones.", "Effects of age and illumination on night driving: a road test.", "Comparing explorative saccade and flicker training in hemianopia: a randomized controlled study.", "Use of prisms for navigation and driving in hemianopic patients.", "Effect of a walking aid on disability, oxygenation, and breathlessness in patients with chronic airflow limitation.", "A randomized controlled trial to evaluate the relative efficacy of adding voluntary counseling and testing (VCT) to information dissemination in reducing HIV-related risk behaviors among Hong Kong male cross-border truck drivers." ]

[ "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.", "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.", "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 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.", "Patients with homonymous hemianopia are disabled on everyday exploratory activities. We examined whether explorative saccade training (EST), compared with flicker-stimulation training (FT), would selectively improve saccadic behavior on the patients' blind side and benefit performance on natural exploratory tasks.\n Twenty-eight hemianopic patients were randomly assigned to distinct groups performing for 6 weeks either EST (a digit-search task) or FT (blind-hemifield stimulation by flickering letters). Outcome variables (response times [RTs] during natural search, number of fixations during natural scene exploration, fixation stability, visual fields, and quality-of-life scores) were collected before, directly after, and 6 weeks after training.\n EST yielded a reduced (post/pre, 47%) digit-search RT for the blind side. Natural search RT decreased (post/pre, 23%) on the blind side but not on the seeing side. After FT, both sides' RT remained unchanged. Only with EST did the number of fixations during natural scene exploration increase toward the blind and decrease on the seeing side (follow-up/pre difference, 238%). Even with the target located on the seeing side, after EST more fixations occurred toward the blind side. The EST group showed decreased (post/pre, 43%) fixation stability and increased (post/pre, 482%) asymmetry of fixations toward the blind side. Visual field size remained constant after both treatments. EST patients reported improvements in social domain.\n Explorative saccade training selectively improves saccadic behavior, natural search, and scene exploration on the blind side. Flicker-stimulation training does not improve saccadic behavior or visual fields. The findings show substantial benefits of compensatory exploration training, including subjective improvements in mastering daily-life activities, in a randomized controlled trial.", "(1) To compare the outcomes of orientation and mobility and driving training with Fresnel prisms and the Gottlieb Visual Field Awareness System for patients with homonymous hemianopsia, and (2) To determine whether the patients continue to use the optical enhancement devices at a 2-year follow-up point.\n Patients with homonymous hemianopsia were provided with a rehabilitation program where they were fitted with prism lenses and trained to use them for navigation and driving. Telephone interviews were used to obtain information about device usage 2 years following the completion of the training program.\n Patients' performance was compared with a test-retest criterion in the visual skills areas of recognition, mobility, peripheral detection, scanning, tracking, and visual memory. Patients with hemianopic loss showed improvements in all of the visual skills categories, ranging from the highest improvements of 26% of tasks improved in the mobility category to 13% in the recognition category. The majority of the hemianopic patients reported using the devices at the 2-year follow-up interview.\n The patients with homonymous hemianopsia showed improvements in visual functioning using prism lenses, although these improvements were smaller than those found in previous studies with central or bilateral peripheral vision loss groups who were trained to use other optical enhancement devices for navigation and driving using a similar curriculum. However, given the evidence of increased risk of accidents for patients with peripheral vision loss, the safety of peripheral enhancement devices for driving must be thoroughly evaluated before their impact on public safety is known.", "This study assessed the effect of a wheeled walking aid on disability, oxygenation, and breathlessness in patients with severe disability secondary to chronic irreversible airflow limitation.\n Eleven subjects with chronic irreversible airflow limitation, mean forced expired volume in 1 second (FEV1) 0.71 L +/- .33 L, were studied. Subjects performed four 6-minute walk tests, two on each of two study days, twice unaided and twice with the assistance of a wheeled walking aid. A randomized cross-over design was used. All subjects were oriented to 6-minute walk tests, use of bronchodilators was controlled, and standard encouragement was given during each walk test. Outcome measures were the distance walked in 6 minutes, change in oxyhemoglobin saturation during the walk, and breathlessness using a modified Borg Scale.\n The use of a wheeled walker resulted in a significant increase in 6-minute walking distance, a significant reduction in hypoxemia with walking and a significant reduction in breathlessness during the walk test.\n The use of a wheeled walker resulted in significant decreases in disability, hypoxemia, and breathlessness during a 6-minute walk test. By reducing disability and breathlessness, a wheeled walker may improve quality of life in individuals with severe impairment in lung function.", "Mobile populations are vulnerable to contracting HIV. The present study aims to evaluate the relative efficacy of the voluntary counseling and testing plus information dissemination (VCT-ID) approach versus the information dissemination (ID) approach for promoting HIV preventive behaviors in a mobile population, cross-border truck drivers. A total of 301 adult male cross-border truck drivers who self-reported having had sex with female sex workers (FSW) or non-regular sex partners (NRPs) in mainland China in the last 12 months were recruited and randomized into the VCT-ID intervention group (Group I) or ID control group (Group C). Anonymous structured questionnaires, administered through a computer-assisted method, were used to collect data. At the follow-up survey (about 8-9 weeks since the baseline survey), Group I participants, as compared to Group C participants, were more likely to be consistent condom users when having sex with FSW (85.5% versus 68.5%, p<0.05) and with NRP (54.8% versus 36.4%, p<0.1), more knowledgeable about HIV, and were less likely to have contracted sexually transmitted diseases (STD) in the last two months. The VCT-ID approach is shown to be more efficacious than the ID approach in promoting safer sex and HIV-related knowledge among local cross-border truck drivers. Feasibility of providing voluntary counseling and testing (VCT) services at locations which are convenient to the target population is demonstrated. It also shows that VCT services can be used as a means of HIV prevention. The findings of this study resulted in up-scaled VCT services for the local target population." ]

[ "16084925", "18237352", "15823886", "11242721", "15113492", "18838727", "15249520", "22032247", "16602835", "19707060", "19775439" ]

[ "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "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.", "Comparison of an enhanced versus a written feedback model on the management of Medicare inpatients with venous thrombosis.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "The effect of a quality improvement collaborative to improve antimicrobial prophylaxis in surgical patients: a randomized trial.", "Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Implementing collaborative care for depression treatment in primary care: a cluster randomized evaluation of a quality improvement practice redesign.", "Participatory supervision model: building health promotion capacity among health officers and the community.", "The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies." ]

[ "This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible, acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff. Undertaken in five acute hospital sites in the East Midlands UK, 22 multidisciplinary teams were randomised to either an intervention or control arm. Employing mixed methods, a range of outcomes, including collaborative behaviour, was measured. The intervention was feasible and acceptable to staff. Involvement in the facilitated programme had a positive impact on self-reported knowledge (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post-intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post-intervention), appeared to have some influence on improving self-reported (P<0.05 post-intervention) and observed collaborative behaviour (P=0.01) and led to better quality audit resulting in measurable improvements to care. Improved collaborative behaviour may have resulted from an increase in assertive behaviour by nurses. Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main (phase 111) trials are undertaken.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "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.", "A multistate randomized study conducted under the Health Care Financing Administration's (HCFA's) Health Care Quality Improvement Program (HCQIP) offered the opportunity to compare the effect of a written feedback intervention (WFI) with that of an enhanced feedback intervention (EFI) on improving the anticoagulant management of Medicare beneficiaries who present to the hospital with venous thromboembolic disease.\n Twenty-nine hospitals in five states were randomly assigned to receive written hospital-specific feedback (WFI) of feedback enhanced by the participation of a trained physician, quality improvement tools, and an Anticoagulant Management of Venous Thrombosis (AMVT) project liaison (EFI). Differences in the performance of five quality indicators between baseline and remeasurement were assessed. Quality managers were interviewed to determine perceptions of project implementation.\n No significant differences in the change from baseline to remeasurement were found between the two intervention groups. Significant improvement in one indicator and significant decline in two indicators were found for one or both groups. Yet 59% of all quality managers perceived the AMVT project as being successful to very successful, and more EFI quality managers perceived success than did WFI managers (71% versus 40%). In the majority of EFI hospitals, physician liaisons played an important role in project implementation.\n Study results indicated that the addition of a physician liaison, quality improvement tools, and a project liaison did not provide incremental value to hospital-specific feedback for improving quality of care. Future studies with larger sample sizes, lengthier follow-up periods, and interventions that include more of the elements shown to affect practice behavior change are needed to identify an optimal feedback model for use by external quality management organizations.", "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "Quality improvement collaboratives are used to improve health care quality, but their efficacy remains controversial.\n To assess the effects of a quality improvement collaborative on preoperative antimicrobial prophylaxis.\n Longitudinal cluster randomized trial, with the quality improvement collaborative as the intervention.\n United States.\n 44 acute care hospitals, each of which randomly sampled approximately 100 selected surgical cases (cardiac, hip or knee replacement, and hysterectomy) at both the baseline and remeasurement phases.\n All hospitals received a comparative feedback report. Hospitals randomly assigned to the intervention group (n = 22) participated in a quality improvement collaborative comprising 2 in-person meetings led by experts, monthly teleconferences, and receipt of supplemental materials over 9 months.\n Change in the proportion of patients receiving at least 1 antibiotic dose within 60 minutes of surgery (primary outcome) and change in the proportions of patients given any antibiotics, given antibiotics for 24 hours or less, given an appropriate drug, and given a single preoperative dose and receipt of any of the 5 measures (secondary outcome).\n The groups did not differ in the change in proportion of patients who received a properly timed antimicrobial prophylaxis dose (-3.8 percentage points [95% CI, -13.9 to 6.2 percentage points]) after adjustment for region, hospital size, and surgery type. Similarly, the groups did not differ in individual measures of antibiotic duration; use of appropriate drug; receipt of a single preoperative dose; or an all-or-none measure combining timing, duration, and selection.\n Hospitals volunteered for the effort, thereby resulting in selection for participants who were motivated to change. Implementation of the surgical infection prevention measure reporting requirements by the Centers for Medicare & Medicaid Services and The Joint Commission may have motivated improvement in prophylaxis performance.\n At a time of heightened national attention toward measures of antimicrobial prophylaxis performance, the trial did not demonstrate a benefit of participation in a quality improvement collaborative over performance feedback for improvement of these measures.", "A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients.\n The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician.\n Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops.\n These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.", "Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness.\n The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM.For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months.\n Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003).\n Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed.\n ClinicalTrials.gov: NCT00105820.", "The Thai traditional health supervision model has been developed since 1991. However, many supervisors lack supervisory knowledge and skills. This study aimed to compare and identify the strengths and challenges of two different supervision models, in order to determine their effects on enhancing the health promotion capacity of health officers in two primary care units (PCU) in Chiang Mai Province, northern Thailand.\n The two models were implemented at two PCU in one semi-district, Chiang Mai Province, over a six-month period. The first model involved supervisors from the district level, with the full participation of health officers at the sub-district level. The second model was designed with the addition of community involvement in the supervision process. Before implementing the models, the district supervisors attended a retraining course to enhance their supervisory knowledge and ability. Questionnaires were used to assess health officers' job satisfaction, clients' perceived service quality and care satisfaction. Semi-structured interviews and qualitative observations were used to explore the involvement of health officers and the community, and to determine the strengths and challenges of each supervisory model.\n Both before and after the intervention, the PCU health officers appeared to have good and comparable job satisfaction levels. Bivariate analysis indicated that after the intervention, both supervisory models appeared effective in terms of clients' perceived service quality and satisfaction with care, among those who utilized the PCU. However, the second model, which allowed the community to participate in the supervision process, achieved better results. The qualitative findings suggested that the involvement of health officers caused a rapid change and improvement after the supervision. The involvement of the community helped the community itself to identify problems and formulate alternatives to meet the community's needs.\n This study shows positive outcomes for two forms of participatory supervision in a rural setting. There appear to be additional positive outcomes for the model that involved community participation. To ensure successful implementation, several issues, such as the supervisor's knowledge and ability, health officer workload and supervisory communication skills, need to be improved.", "Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO.\n The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin.\n The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1).\n This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?" ]

[ "20233384" ]

[ "Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions." ]

[ "Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).\n Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.\n Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome\n The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions." ]

[ "15684225", "12411847", "14718327", "9168368" ]

[ "Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies.", "Hypodermoclysis for control of dehydration in terminal-stage cancer.", "The comprehensive care team: a controlled trial of outpatient palliative medicine consultation.", "A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation." ]

[ "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.", "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.", "Little is known about the use of palliative care for outpatients who continue to pursue treatment of their underlying disease or whether outpatient palliative medicine consultation teams improve clinical outcomes.\n We conducted a year-long controlled trial involving 50 intervention patients and 40 control patients in a general medicine outpatient clinic. Primary care physicians referred patients with advanced congestive heart failure, chronic obstructive pulmonary disease, or cancer who had a prognosis ranging from 1 to 5 years. In the intervention group, the primary care physicians received multiple palliative care team consultations, and patients received advance care planning, psychosocial support, and family caregiver training. Clinical and health care utilization outcomes were assessed at 6 and 12 months.\n Groups were similar at baseline. Similar numbers of patients died during the study year (P =.63). After the intervention, intervention group patients had less dyspnea (P =.01) and anxiety (P =.05) and improved sleep quality (P =.05) and spiritual well-being (P =.007), but no change in pain (P =.41), depression (P =.28), quality of life (P =.43), or satisfaction with care (P =.26). Few patients received recommended analgesic or antidepressant medications. Intervention patients had decreased primary care (P =.03) and urgent care visits (P =.04) without an increase in emergency department visits, specialty clinic visits, hospitalizations, or number of days in the hospital. There were no differences in charges (P =.80).\n Consultation by a palliative medicine team led to improved patient outcomes in dyspnea, anxiety, and spiritual well-being, but failed to improve pain or depression. Palliative care for seriously ill outpatients can be effective, but barriers to implementation must be explored.", "Outpatient parenteral nutrition (PN) is often given to marrow transplant recipients after high-dose chemoradiotherapy until the resumption of adequate oral intake; however, it may adversely prolong resumption or oral calorie intake by contributing to early satiety.\n A double-blind, randomized study compared standard PN (final concentration 25% dextrose, 5% amino acids) with a hydration solution (5% dextrose) during the first 28 days of outpatient treatment. Patients were eligible for the study if they were > or = 2 years of age, < 65 days posttransplant, had < 70% oral caloric intake at hospital discharge, and required < or = 10 U insulin/L PN. Solutions were provided until the patient's oral intake met > or = 85% caloric requirements for 3 consecutive days.\n Two hundred fifty-eight marrow transplant recipients (128, PN and 130, hydration solution) were studied. Age, donor type, and diagnoses were similar in the two groups. Time to resumption of > or = 85% oral caloric intake was 6 days sooner in the hydration group than in the PN group (median 10 vs 16 days, respectively; p = .049). When adjusting for sex, age, donor type, total body irradiation, previous oral intake, acute graft-versus-host disease, and prednisone therapy, the hydration group resumed oral intake sooner than the PN group (relative risk = 1.51; 95% confidence interval [CI] 1.04 to 2.19; p = .029). The percentage of weight change from pretransplant values, adjusted for the above covariates and the number of weeks of treatment, indicated that the hydration solution group lost weight (4.63%) compared with the PN group (1.27%) after 4 weeks of therapy (p = .004). Rates of hospital readmissions, relapse of malignancy, and survival did not differ between the two treatment groups.\n We conclude that outpatient PN delays resumption of oral intake and that its replacement with hydration solution does not result in adverse patient outcome." ]

[ "12444816", "9809861", "19907043" ]

[ "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.", "Outcome reporting in industry-sponsored trials of gabapentin for off-label use." ]

[ "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.", "There is good evidence of selective outcome reporting in published reports of randomized trials.\n We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.\n We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.\n We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.\n 2009 Massachusetts Medical Society" ]

[ "16467702", "8323451", "12665269", "8703248", "359091", "8760776", "18415831" ]

[ "A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis.", "[Effects of high doses of beclomethasone dipropionate in bronchial asthma].", "The clinical efficacy of fluticasone propionate (Fluvent) compared with beclomethasone dipropionates (Becotide) in patients with mild to moderate brochial asthma at the University College Hospital, Ibadan, Nigeria.", "Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma.", "Beclomethasone dipropionate dry-powder inhalation compared with conventional aerosol in chronic asthma.", "Fluticasone propionate compared with theophylline for mild-to-moderate asthma.", "Effect of feedback letters to physicians and pharmacists on the appropriate use of medication in the treatment of asthma." ]

[ "The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study.\n The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin.\n There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P<.05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients.\n These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.", "To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.", "This open, randomized trial was conducted at the Medical Out patient Department of University College Hospital, Nigeria to compare the clinical efficacy of Beclomethasome dipropionate (Becotide) with Fluticasone propionate (Fluvent) in patients with mild to moderate bronchial asthma. The study was performed as a week screening, 8-weeks open comparative clinical trial involving Fluticasone propionate (Fluvent) at a daily dose of 22 microg and Beclomethasone Dipropionate (Becotide) at a dose of 400 microg daily delivered through pressurized metered-dose inhaler (pMDI). The main objective of this study is to assess the efficacy of Fluvent in patients with mild to moderate asthma compared to Becotide. At the second visit (end of 1 week), 10 patients were given either Becotide of Fluvent but all were maintained on as needed beta2agonist (Salbutamol inhaler) therapy throughout the study. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEFR and FEV1) while safety was assessed by adverse event experiences. The baseline characteristics of the patients randomized into the two drug groups were comparable and of no statistical significance. The changes in the pulmonary function tests as well as the reduction in the asthma symptoms suggest a statistically significant improvement in the asthma status of the patients. However, these changes were more rapid among the patients using Fluvent. Also, there was higher percentage decline in the episodes of asthma symptoms either in the morning, day or night in the Fluvent group than Becotide group. The drugs were well tolerated and no adverse event was noticed on any of the patients. We therefore concluded that Fluvent would be more efficacious than Becotide in the treatment of Asthma.", "We studied the effect of inhaled budesonide on bronchial hyperresponsiveness (BHR) in twenty mild asthmatic patients. The study was conducted as a randomized, double-blind, placebo-controlled study. Before entering the study, the patients performed methacholine inhalation challenge (MIC) using a reservoir method to assess BHR. Then, they were randomly allocated to receive budesonide turbuhaler (200 micrograms/dose) or placebo turbuhaler two inhalations, twice daily for eight weeks. During the study, each patient recorded daily asthma score and daily number of puffs of beta 2 agonist and they were assessed at weeks 4 and 8. At the end of the treatment, MIC was repeated again. Patients receiving budesonide showed a significant improvement in airway responsiveness compared with those receiving placebo (p < 0.05). They also showed a significant improvement in asthma severity score and a significant decrease in beta 2 agonist bronchodilator use. This study also suggested that inhaled corticosteroids may be the primary treatment in patients, even with mild asthmatic and well-controlled symptoms.", "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.", "The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma.\n The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma.\n In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms.\n Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%).\n Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.", "Suboptimal medication treatment of asthma has been reported. More specifically, short-acting beta 2-agonists are overused, while inhaled corticosteroids are underused. This can be related in part to poor adherence by patients to the prescribed regimen and to professionals' failure to comply with practice guidelines. Feedback seems to have an effect on professional practices related to medication use.\n To assess the impact of feedback letters to physicians and pharmacists on their patients' appropriate use of asthma medication.\n Two randomized trials were set up in the province of Quebec, Canada: one with physicians and another with pharmacists. A sample of voluntary physicians and pharmacists was randomly assigned to either the experimental group or to the control group. Those in the experimental groups received three consecutive feedback letters over a 9-month period summarizing the asthma medications acquired by their patients over the preceding year. The feedback focused on short-acting beta 2-agonists, long-acting beta 2-agonists and antileukotrienes and provided information on compliance with five appropriate-use criteria. Pharmacists received aggregate profiles and individual profiles with patients' names, while most physicians received aggregate profiles for all their eligible patients. Each mailing also included a pamphlet that summarized practice guidelines on asthma treatment.\n Seventy-one physicians and 60 pharmacists participated in the study. Physicians who received the feedback letters did not differ from those in the control group in terms of their proportion of prescriptions compliant with the criteria, either before the feedback or after it (p > 0.05). The before-after difference was also similar between groups. The same was true for pharmacists. However, although the before-after difference for criteria 1 (frequency of use of short-acting beta 2-agonists) and 2 (frequency of use of long-acting beta 2-agonists) did not reach the usual statistical significance threshold of 0.05, the p value was under 0.10.\n As designed in this study, feedback provided to physicians did not improve the appropriate use of asthma medication. However, feedback to pharmacists is promising, especially when including patients' names so that pharmacists can intervene more specifically." ]

[ "11115031", "18410212", "12038883" ]

[ "Promoting secure attachment, maternal mood and child health in a vulnerable population: a randomized controlled trial.", "Establishing family foundations: intervention effects on coparenting, parent/infant well-being, and parent-child relations.", "A randomized, controlled trial of a community-based support program for families of children with chronic illness: pediatric outcomes." ]

[ "To evaluate the efficacy of an early home-based intervention on the quality of maternal-infant attachment, maternal mood and child health parameters in a cohort of vulnerable families.\n A total of 181 families were recruited to the study in the immediate postnatal period on the basis of a self report questionnaire relating to known family vulnerability factors. Families were assigned randomly to intervention (90), or control (91) groups. The intervention group received a series of home visits from a child health nurse (weekly to 6 weeks, fortnightly to 3 months), with a subgroup receiving home based short-term dynamic therapy from a social worker. Parent/family function was assessed at inception and at 4 months by the Parenting Stress Index and the Edinburgh Post Natal Depression Scale. At 4 months the quality of the home environment was assessed, utilizing the Home Observation for Measurement of the Environment Inventory, as were child and family health parameters and satisfaction with the community child health service.\n At 4 month follow-up, 160 families (80 intervention, 80 control) were available for assessment. The intervention improved family functioning at 4 months. All aspects of the home environment, including the quality of maternal-infant attachment and mothers' relationship with their child, were significantly enhanced. In particular, significant and positive differences were found in parenting with the intervention group feeling less restrictions imposed by the parenting role, greater sense of competence in parenting, greater acceptability of the child, and the child being more likely to provide positive reinforcement to the parent. Early differences in maternal mood were not maintained at 4 months. Various child health parameters were enhanced including immunization status, fewer parent-reported injuries and bruising, and researcher confirmed lack of smoking in the house or around the infant. The families were consistently more satisfied with their community health service.\n This form of early home based intervention targeted to vulnerable families promotes an environment conducive for infant mental and general health and hence long-term psychological and physical well-being, and is highly valued by the families who receive it.", "This study investigated the ability of a theoretically driven, psychosocial prevention program implemented through childbirth education programs to enhance the coparental relationship, parental mental health, the parent-child relationship, and infant emotional and physiological regulation. A sample of 169 heterosexual, adult couples who were expecting their 1st child was randomized to intervention and control conditions. The intervention families participated in Family Foundations, a series of 8 classes, delivered before and after birth, that was designed as a universal prevention program (i.e., it was applicable to all couples, not just those at high risk). Intent-to-treat analyses indicated significant program effects on coparental support, maternal depression and anxiety, distress in the parent-child relationship, and several indicators of infant regulation. Intervention effects were not moderated by income, but greater positive impact of the program was found for lower educated parents and for families with a father who reported higher levels of insecure attachment in close relationships. These findings support the view that coparenting is a potentially malleable intervention target that may influence family relationships as well as parent and child well-being.\n (c) 2008 APA, all rights reserved.", "Children with chronic illnesses have a heightened risk for mental health problems.\n To develop, implement, and evaluate child outcomes of a 15-month, community-based, family-support intervention designed to reduce risk for poor adjustment and mental health problems in children with 1 of 4 chronic illnesses (diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma) and their mothers.\n Randomized, controlled clinical trial design with multiple measures of mental health based on both child and parent reports taken 1 year apart.\n Community-based intervention linked to subspecialty and general pediatric clinics and practices in Baltimore, Md.\n One hundred thirty-six mothers and children aged 7 to 11 years with diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma.\n The program, provided by \"experienced mothers\" and child life specialists, included telephone contacts, face-to-face visits, and special family events.\n Outcomes were measured using the following instruments: the Personal Adjustment and Role Skills Scale III, the Children's Depression Inventory, the Revised Children's Manifest Anxiety Scale, and the Self-Perception Profile for Children.\n The experimental group's mean adjustment score increased over the intervention period while the control group's mean adjustment score decreased. Analysis of variance demonstrated that the intervention had a significant main effect on postintervention adjustment controlling for baseline scores (P =.01). Using a cutoff score indicating maladjustment, the percentage of experimental group children in the maladjustment range fell from 19% at baseline to 10% after the intervention; the percentage of control group children in the maladjustment range rose from 15% at baseline to 21% after the intervention. The effect of the intervention was more pronounced for children who had low physical self-esteem than for those who had moderate to high physical self-esteem at the beginning of the program.\n Our results demonstrate modest positive effects of a family support intervention in promoting the adjustment of children with selective chronic health conditions. Including child life specialists in a community-based intervention may be especially salient for children with chronic illnesses who have low physical self-esteem. The intervention had a similar outcome for all diagnostic groups, suggesting that it could be effective for children with any chronic illness and implemented in a variety of pediatric settings." ]

[ "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." ]

[ "14682412", "19138505", "10421835", "10630654", "12149529", "11243949" ]

[ "Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study.", "Fluticasone and N-acetylcysteine in primary care patients with COPD or chronic bronchitis.", "A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease.", "The effect of a respiratory home nurse intervention in patients with chronic obstructive pulmonary disease (COPD).", "Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness.", "Systemic glucocorticoids in severe exacerbations of COPD." ]

[ "Early treatment with inhaled corticosteroids may prevent progression of irreversible obstruction in COPD, especially in patients with bronchial hyperresponsiveness. We investigated the clinical effects of early introduction of inhaled steroids in subjects showing early signs and symptoms of COPD without a prior clinical diagnosis.\n Study subjects were detected in a general population screening and monitoring program. Those with a moderately accelerated annual FEV1 decline and persistent respiratory symptoms were invited to participate in a 2-year randomized controlled trial comparing fluticasone propionate DPI 250 microg b.i.d. with placebo. Pre- and post-bronchodilator (BD) FEV1, PC20 histamine, functional status (COOP/WONCA charts) and occurrence of exacerbations were periodically assessed. Subjects recorded respiratory symptoms. Post-BD FEV1 decline served as the main outcome. Multivariable repeated measurements analysis techniques were applied.\n 48 subjects were randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV1 had increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV1 with 174 ml (SE 90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent post-BD and pre-BD FEV1 decline were not beneficially modified by fluticasone treatment. There were no statistically significant differences in respiratory symptoms, functional status, or exacerbations favoring fluticasone. Subgroup analysis indicated that the presence of bronchial hyperresponsiveness modified the initial FEV1 response on fluticasone, but not the subsequent annual FEV1 decline.\n Early initiation of inhaled steroid treatment does not seem to affect the progressive deterioration of lung function or other respiratory health outcomes in subjects with early signs and symptoms of COPD. In subjects at risk for, or in an early stage of COPD, long-term inhaled steroid treatment should not be based on a single spirometric evaluation after 3 months.", "Increased oxidative stress and bronchial inflammation are important mechanisms in the pathophysiology of COPD.\n To investigate whether treatment with the inhaled corticosteroid fluticasone propionate (FP) or the anti-oxidative agent N-acetylcysteine (NAC) are effective in primary care patients.\n The study was a 3-year placebo-controlled randomised controlled trial preceded by a 3-month washout and 2-week prednisolone pre-treatment. Patients were (ex-)smokers with chronic bronchitis or COPD. Interventions were inhaled FP 500microg b.i.d., oral NAC 600mg o.d., or placebo. Exacerbation rate and quality of life measured with the Chronic Respiratory Questionnaire (CRQ) were the primary outcomes, FEV(1) decline and respiratory symptoms secondary outcomes.\n 286 patients recruited from 44 general practices were randomised. Exacerbation rate was 1.35 times higher for NAC (p=0.054) and 1.30 times higher for FP (p=0.095) compared with placebo. CRQ total scores did not differ between NAC (p=0.306) or FP (p=0.581) treatment compared to placebo. Annual postbronchodilator FEV(1) decline was 64mL [SD 5.4] for NAC [p=0.569 versus placebo], 59mL [SD 5.7] for FP [p=0.935], and 60mL [SD 5.4] for placebo.\n No beneficial treatment effects for either high-dosed inhaled fluticasone propionate or oral N-acetylcysteine were observed in our study population of patients with COPD or chronic bronchitis.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV1 in individual patients calculated over this period. Ninety-eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV1, measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long-term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV1 returned to normal levels expected from age-related decline, and hence such treatment combined with other strategies may well have a significant role in the long-term treatment of this condition.", "Chronic obstructive pulmomary disease (COPD) is associated with substantial mortality, morbidity, and costs to the health care system. With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services, for conditions such as COPD.\n To determine the effectiveness of an outreach respiratory nurse in a shared care approach, with collaboration between general practitioners and hospital services, in the management of patients with severe COPD.\n Patients with severe COPD attending The Queen Elizabeth Hospital, Adelaide participated in a randomised controlled trial of a home based nursing intervention (HBNI) over 12 months with outcome measures including mortality rate, hospital service utilisation, FEV1 and health related quality of life (HRQL) using a modified Dartmouth Primary Care Co-operative Quality of Life questionnaire.\n There were 48 subjects in each study arm, with no differences in mortality rate (eight deaths in the HBNI group and seven in the control group), hospital admissions, length of stay, number of outpatient and Emergency Service visits. The study had inadequate follow-up of FEV1 and HRQL within the control group. Within the HBNI group, a small improvement in HRQL (in three of ten indices measured) was demonstrated, despite a deterioration in FEV1 (11% reduction, p=0.04) compared to baseline. Quality of life of HBNI subjects' carers did not change.\n An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR).\n Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC(20) for histamine of <or=8 mg/ml. Patients received either 2 x 500 microg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls.\n In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV(1)) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV(1)/FVC, and maximal expiratory flows at 50% and 25% FVC (MEF(50), MEF(25)) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation.\n In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.", "This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure.\n Prospective, randomized, single-blind study.\n Tertiary-care center.\n Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study.\n Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group.\n In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates." ]

[ "21714641", "1991274", "6734291", "2776873", "15013579", "9428212" ]

[ "Reduced lung-cancer mortality with low-dose computed tomographic screening.", "Screening for lung cancer. A critique of the Mayo Lung Project.", "Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York.", "A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR.", "Effectiveness of smoking cessation self-help materials in a lung cancer screening population.", "Yearly colonoscopy, liver CT, and chest radiography do not influence 5-year survival of colorectal cancer patients." ]

[ "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.).", "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 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.", "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.", "Randomized controlled trials of smoking interventions have not been well-documented for lung cancer screening populations. In this study, we randomly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT (SCTS) for lung cancer screening to receive either standard written self-help materials or a written list of Internet resources for smoking cessation. At the 1-year follow-up, more of the subjects receiving Internet-based resources reported making a stop attempt (68% versus 48%, P=0.011). However, there were no statistically significant differences in 7-day point prevalence quit rates (5% versus 10%) or advancement in motivational readiness to stop smoking (27% versus 30%), respectively, between the groups. Clearly, more investigation is warranted into how to tailor smoking interventions for cancer screening participants.", "Guidelines on the type and frequency of follow-up of patients after curative surgery for colorectal cancer are unclear. The aim of this study was to determine the survival benefit of a planned follow-up program.\n Three hundred twenty-five patients who underwent curative resection of colorectal cancer were prospectively randomized to either intensive or standard follow-up. After stratification according to Dukes' stage and site in the colon or rectum, patients were randomized to intensive follow-up of yearly colonoscopy, computerized tomography (CT) of the liver, and chest radiography and clinical review and simple screening vs. structured clinical review and simple screening tests only.\n On completion of 5-year follow-up, there was no significant difference in survival between the two groups. Yearly colonoscopy failed to detect any asymptomatic local recurrences. Only one asymptomatic curable metachronous colon tumor was detected. Liver CT resulted in earlier detection of hepatic metastases but did not increase the number of curative hepatectomies. Only 1 patient had an asymptomatic CT-detected liver metastasis, and another had an asymptomatic chest radiography-detected lung metastasis. Both had curative resections.\n Yearly colonoscopy, liver CT, and chest radiography will not improve survival from colorectal cancer when added to symptom and simple screening review." ]

[ "2064291", "8492040", "7857145", "9738217" ]

[ "[The best anastomoses after colonic resection].", "Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial.", "Comparison of manually constructed and stapled anastomoses in colorectal surgery. West of Scotland and Highland Anastomosis Study Group.", "[Is the stapled suture in visceral surgery still justified? A prospective controlled, randomized study of cost effectiveness of manual and stapler suture]." ]

[ "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.", "440 patients were prospectively enrolled in a randomized, multicenter trial to compare 4 types of manual (84 interrupted end-to-end, 77 continuous end-to-end, 82 interrupted end-to-side, and 91 continuous end-to-side) (polyglycolic derived suture) and 1 type of stapled (106 side-to-side with GIA+TA devices) ileocolonic anastomosis after right hemicolectomy for carcinoma. The trial was designed according to Schwartz' pragmatic formulation. All 5 groups were well-matched, except for a lower rate of intraoperative sepsis in the stapled group (P < 0.02). The main end point was anastomotic leakage detected clinically or by routine sodium diatrizoate enema on the 8-10th postoperative day. Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages (2.8%) than all the other techniques combined (8.3%). In spite of the fact that staples are approximately ten times more expensive, our results suggest performing side-to-side (GIA+TA) mechanical anastomosis after right resection for carcinoma.", "The authors compared both the initial and the long-term outcomes of patients undergoing stapled and sutured colorectal anastomoses.\n Sutured and stapled large bowel anastomoses are perceived to be equally safe, but concern has been raised about increased rates of tumor recurrence with the use of stapling instruments.\n The outcome of patients with sutured and stapled colorectal anastomoses were compared in a prospective, multicenter, randomized study. Factors affecting long-term outcomes were assessed by both univariate and multivariate analysis.\n Seven hundred thirty-two patients were recruited. There was a significant increase in radiologic leakage in the sutured group (14.4% vs. 5.2%, p < 0.05), but there was no difference in clinical anastomotic leak rates, morbidity, or postoperative mortality. Tumor recurrence and cancer-specific mortality were higher in the sutured patients (7.5% and 6.7%, respectively) and in patients with anastomotic leaks.\n This study shows that suturing or stapling are equally safe in large bowel surgery. However, it also shows a long-term benefit of stapling in colorectal cancer patients.", "Hospitals are facing increasing economic pressure. It therefore seems necessary to evaluate the efficiency and effectiveness of medical or surgical interventions. In this study 324 anastomoses (167 stapled and 157 hand-sewn) were performed after randomization during 200 elective operations [20.5% gastrectomies, 14% gastric resections (Billroth II), 15% Whipple's procedures, 4% segmental colonic resections, 18% right-sided hemicolectomies, 4% left-sided hemicolectomies, 22% sigmoid- or anterior rectal resections, 2.5% total colectomies with pouch-anal anastomoses] in 200 patients. Postoperative motility (time to full oral diet, time with naso-gastric tube) and hospitalization were comparable in both groups. Anastomotic insufficiency was observed in 2.1% of all patients, five after stapled and two after hand-sewn anastomoses. Hospital mortality was 1.5%. All stapled anastomoses were performed significantly (P < 0.001) faster. However, the cost of material for these anastomoses was significantly (P < 0.001) higher, resulting in significantly higher total costs for reconstruction. The time saving for the reconstruction did not influence the total operative time (except for stapled gastrectomy). Therefore, all operations with stapled reconstruction were more expensive than those with sutured reconstruction. The difference was significant for the gastrectomy (P < 0.01), colonic resection (P < 0.01) and sigmoid and rectal resection (P < 0.001) groups. Stapled and sutured anastomoses are equally effective. Stapled anastomoses are not efficient, however, and should be reserved for individual indications." ]

[ "1748145", "18426821", "17391168", "15334791", "17392540", "11678974", "10063324", "11772907", "12453948", "16448519", "15606381", "15612515", "19307526" ]

[ "Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles.", "Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes.", "Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial.", "Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin.", "Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study.", "Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients.", "[Gliclazide and metformin combination in patients with type 2 diabetes. Preliminary data].", "Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.", "Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects.", "Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.", "Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial.", "[Efficacy and safety of glimepiride plus metformin in a single presentation, as combined therapy, in patients with type 2 diabetes mellitus and secondary failure to glibenclamide, as monotherapy].", "Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus." ]

[ "Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year. The drugs had an equivalent effect on glycaemic control, but, in contrast to glibenclamide, metformin reduced body weight. Neither drug affected triglycerides, total- and LDL-cholesterol or C-peptide. Metformin caused a slight elevation of HDL-cholesterol (P less than 0.05). No serious adverse effects were observed. The results show that oral hypoglycaemic agents are not associated with undesirable effects on lipids and lipoproteins.", "In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients.\n Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index< or =27 kg/m(2)) insulin-naïve T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions.\n Levels of tumour necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6, fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment effects.\n In non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments.", "Metformin is the 'drug-of-first-choice' in obese patients with type 2 diabetes mellitus (T2DM) due to its antihyperglycaemic and cardiovascular protective potentials. In non-obese patients with T2DM, insulin secretagogues are empirically used as first choice. In this investigator-initiated trial, we evaluated the effect of metformin vs. an insulin secretagogue, repaglinide on glycaemic regulation and markers of inflammation and insulin sensitivity in non-obese patients with T2DM.\n A single-centre, double-masked, double-dummy, crossover study during 2 x 4 months involved 96 non-obese (body mass index < or = 27 kg/m(2)) insulin-naïve patients with T2DM. At enrolment, previous oral hypoglycaemic agents (OHA) were stopped and patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either repaglinide 2 mg thrice daily followed by metformin 1 g twice daily or vice versa each during 4 months with 1-month washout between interventions.\n End-of-treatment levels of haemoglobin A(1c) (HbA(1c)), fasting plasma glucose, mean of seven-point home-monitored plasma glucose and fasting levels of high-sensitivity C-reactive protein and adiponectin were not significantly different between treatments. However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide. Both drugs were well tolerated.\n In non-obese patients with T2DM, overall glycaemic regulation was equivalent with less hypoglycaemia during metformin vs. repaglinide treatment for 2 x 4 months. Metformin was more effective targeting non-glycaemic cardiovascular risk markers related to total and abdominal body fat stores as well as fasting insulinaemia. These findings may suggest the use of metformin as the preferred OHA also in non-obese patients with T2DM.", "Patients with Type 2 diabetes (T2DM) are at high risk of morbidity and mortality from cardiovascular complications, and hypoglycaemia increases this risk. Furthermore, other metabolic parameters exacerbate cardiovascular risk in these patients. The aim of the study was to compare the metabolic effects of glimepiride and metformin in patients with T2DM. We evaluated 164 patients with T2DM (80 males, 84 females) in a multicentre, randomised, controlled, open, parallel group study comparing glimepiride with metformin. Eighty-one patients (aged 56+/-10 yr) received glimepiride (3+/-1 mg/d); 83 patients (aged 58+/-9 yr) received metformin (2500+/-500 mg/d). Patients had been diagnosed for < or = 6 months; they were non-smokers; had no hypertension or coronary heart disease; were not taking hypolipidaemic drugs, diuretics, beta-blockers or thyroxin; and had normal renal function. Metabolic parameters were measured after 6 and 12 months of treatment. Glimepiride significantly lowered lipoprotein(a) [Lp(a)] and homocysteine levels (HCT) at 6 and 12 months. Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months. Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin. Glimepiride and metformin also reduced levels of other metabolic parameters in patients with T2DM. In particular, glimepiride significantly reduced HCT, Lp(a), and PAI-1 levels, important metabolic risk factors for atherosclerotic vascular disease. These reductions may be owing to improved glucose metabolism, but it cannot be excluded that these drugs have a direct effect on additional metabolic parameters.", "To compare the efficacy and safety of glimepiride versus metformin in pediatric subjects with type 2 diabetes inadequately controlled with diet and exercise alone or oral monotherapy.\n This 26-week, single-blind, active-controlled, multinational study randomized 285 subjects to receive glimepiride (1-8 mg once daily) or metformin (500-1000 mg twice daily) for 24 weeks. The primary end point was mean change in A1C from baseline to week 24. Safety was assessed by incidence of hypoglycemia and other adverse events.\n Significant reductions from baseline A1C were seen in both the glimepiride (-0.54%, P = 0.001) and metformin (-0.71%, P = 0.0002) groups. A total of 42.4% (56 of 132) and 48.1% (63 of 131) of subjects in the glimepiride and metformin groups, respectively, in the intent-to-treat population achieved A1C <7.0% at week 24. No significant differences were observed between groups in reductions in A1C and self-monitored blood glucose levels, changes in serum lipid concentrations, or hypoglycemia incidence. Significant differences were observed in mean changes from baseline in BMI between groups (0.26 kg/m(2) for glimepiride and -0.33 kg/m(2) for metformin; P = 0.003). The adjusted mean body weight increase was 1.97 kg for glimepiride and 0.55 kg for metformin (P = 0.005). A hypoglycemic episode with blood glucose <50 mg/dl (<2.8 mmol/l) was experienced by 4.9 and 4.2% of glimepiride- and metformin-treated subjects, respectively. A single severe hypoglycemic event occurred in each group.\n Glimepiride reduced A1C similarly to metformin with greater weight gain, and there was comparable safety over 24 weeks in the treatment of pediatric subjects with type 2 diabetes.", "To compare the effect of glimepiride in combination with metformin with monotherapy of each drug on glycaemic control in Type 2 diabetic patients.\n Randomized, double-blind, double-dummy, parallel-group multicentre study conducted in France. Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily for at least 4 weeks were randomized to either metformin, glimepiride or metformin and glimepiride.\n Three hundred and seventy-two patients aged 56 +/- 8 years were treated for 5 months. Combination treatment was significantly more efficient in controlling HbA1c (% change + 0.07 +/- 1.20 for metformin, + 0.27 +/- 1.10 for glimepiride, -0.74 +/- 0.96 for combination treatment, P < 0.001), fasting blood glucose (FBG) (mmol/l change + 0.8 +/- 0.4 for metformin, + 0.7 +/- 3.1 for glimepiride and -1.8 +/- 2.2 for combination treatment, P < 0.001) and post-prandial blood glucose (PPBG) (mmol/l change + 1.1 +/- 5.9 for metformin, + 0.1 +/- 5.1 for glimepiride and -2.6 +/- 3.9 for combination treatment, P < 0.001) than either glimepiride or metformin alone. There was no significant difference between metformin or glimepiride monotherapy with respect to the change in HbA1c or FBG; however, glimepiride was significantly more effective than metformin in reducing PPBG. The incidence of symptomatic hypoglycaemia was higher in the combination group than in either monotherapy group (P = 0.039).\n Addition of glimepiride to metformin in Type 2 diabetic patients inadequately controlled by metformin alone resulted in superior glycaemic control compared with glimepiride or metformin monotherapy.", "This preliminary study is aimed at the evaluation of the efficacy and tolerability of combined therapy with gliclazide and metformin in the treatment of patients with type 2 diabetes mellitus inadequately controlled with maximal doses of gliclazide.\n A prospective, uncontrolled study, with a follow-up of 3 months, was performed in two Outpatient Diabetes Care Units. Fifty-seven patients affected by type 2 diabetes for at least 5 years, aged 61.0 +/- 3.4 years, with a duration of diabetes of 9.2 +/- 3.9 years, Body Mass Index (BMI) 30.5 +/- 3.7 kg/m2, previously treated with gliclazide 240 mg/day, and with HbA1c > 8.5%, were studied. The patients were treated with gliclazide 120 mg/day and metformin 1500 mg/day for 3 months; HbA1c, 24-hour glycosuria, and fasting and post-prandial glycaemia, were determined at the beginning and at the end of the study.\n After a 3-month treatment, a reduction of fasting and post-prandial glycaemia, glycosuria (15.0 +/- 5.3 versus 5.7 +/- 4.0 g/l, p < 0.01), and HbA1c (9.9 +/- 1.1 versus 8.4 +/- 1.0%, p < 0.01) was observed, while no significant changes occurred in body weight. The treatment was generally well tolerated.\n In conclusion, the combination of gliclazide and metformin, which could theoretically show some advantages over the association of glibenclamide and metformin with regards to lipid and haemorheologic profiles, resulted to be effective and well tolerated in patients with type 2 diabetes inadequately controlled with sulphonylurea monotherapy.", "Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes.\n This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10-16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels > or =7.0 and < or =13.3 mmol/l (> or =126 and < or =240 mg/dl), HbA(1c) > or =7.0%, stimulated C-peptide > or =0.5 nmol/l (> or =1.5 ng/ml), and a BMI > 50th percentile for age.\n Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was -2.4 mmol/l (-42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA(1c) values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin.\n Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.", "Epidemiological studies have implicated increased plasminogen-activated inhibitor 1 (PAI-1) as a marker or predictor of accelerated coronary atherosclerotic disease in type 2 diabetes. We sought to determine whether metabolic control, independent of its oral mode of implementation, affects PAI-1 in patients with marked hyperglycemia.\n A total of 91 subjects were screened, subjected to a 4-week drug washout, and randomized to daily treatment with glipizide GITS (maximum 20 mg, n = 46) or metformin (maximum 2,550 mg, n = 45) as monotherapy. After monotherapy, combination therapy was initiated by adding the second agent to the regimen. Plasma glucose (fasting and postprandial), HbA(1c), fructosamine, and PAI-1 were assayed before and after randomization and sequentially thereafter in all subjects; hepatic glucose output (HGO) and abdominal fat distribution were each measured in a subset of subjects.\n Glycemic control was markedly impaired at baseline (mean HbA(1c) 10.4 +/- 0.2% glipizide GITS; 10.0 +/- 0.2% metformin) but improved comparably with each agent as monotherapy and in combination (P < 0.0001 vs. baseline), as assessed with meal tolerance studies, fructosamine values, and HGO. Body weight and abdominal fat distribution did not change significantly in either group. PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 +/- 12 ng/ml glipizide GITS; 201 +/- 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy.\n When hyperglycemia is profound, increases in PAI-1 are also profound. Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.", "This double-blind study evaluated the efficacy and safety of metformin-glibenclamide tablets vs. metformin plus rosiglitazone therapy in patients with type 2 diabetes inadequately controlled on metformin monotherapy.\n After an open-label, metformin lead-in phase, 318 patients were randomly assigned to treatment based on metformin-glibenclamide 500/2.5 mg tablets (initial daily dose 1000/5 mg) or metformin 500 mg plus rosiglitazone 4 mg (initial daily dose 1000-2000 mg + 4 mg, depending on previous treatment) for 24 weeks. Doses were titrated to achieve the therapeutic glycaemic target. The primary efficacy variable was the change in HbA1C.\n At week 24, metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C (-1.5%) and fasting plasma glucose [-2.6 mmol/l (-46 mg/dl)] than metformin plus rosiglitazone [-1.1%, p < 0.001; -2 mmol/l (-36 mg/dl), p = 0.03]. More patients receiving metformin-glibenclamide attained HbA1C <7.0% than did those in the metformin plus rosiglitazone group (60 vs. 47%) and had fasting plasma glucose levels <7 mmol/l (<126 mg/dl) by week 24 (34 vs. 25%). Both treatments were well tolerated. Frequency of adverse gastrointestinal events was comparable between groups. Four per cent of patients receiving metformin-glibenclamide withdrew because of symptomatic hypoglycaemia contrasted with 3% of patients receiving metformin plus rosiglitazone who withdrew because of persistent hyperglycaemia. Hypoglycaemic events were mild or moderate in intensity and were easily self-managed.\n Metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C and fasting plasma glucose compared with metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.", "The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation.\n The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out.\n The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands).\n Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance <50 mL min(-1), or low plasma cholinesterase (reference value <3.5 units L(-1)), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo).\n The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment.\n When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (-1 to +48; P = 0.06); a decrease in plasma von Willebrand factor of 6% (-10 to -2; P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (-7 to -2; P = 0.0002); a decrease in soluble E-selectin of 6% (-10 to -2; P = 0.008); a decrease in tissue-type plasminogen activator of 16% (-20 to -12; P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (-27 to -10; P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment.\n In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.", "To evaluate the efficacy and safety of glimepiride plus metformin in a single presentation, as combined therapy, in patients with type 2 diabetes mellitus (DM2) with secondary failure to glibenclamide.\n A randomized, double-blind, multicentric trial was carried out in 104 obese patients with DM2, fasting glucose > 140 mg/dL and glycated hemoglobin A1c (A1C) > 8%, in spite of treatment with glibenclamide at maximum doses and medical nutrition therapy for at least the 3 months previous to the study. After randomization, the patients received in titrated way during 3 months one of the following treatments: up to 4 mg of glimepiride, 2 g of metformin or 4 mg of glimepiride plus 2 g of metformin in a single presentation. Efficacy criteria were either a decrease in A1C of 1% or more, or a reduction in A1C of 7% or less. Adverse events were carefully monitored during the study.\n At the end of the study, the decrease in A1C concentration was -0.9 +/- 1.6% (CI 95%: -0.2 to -1.5) in the glimepiride group, -0.7 +/- 2.1% (CI 95%: 0.2 to -1.6) in the metformin group, and -1.3 +/- 1.8 mg/dL (CI 95%: -0.6 to -1.9) in the combined therapy group. The percentage of patients that showed a decrease in AIC of 1% or higher was 35.1, 21.2 and 47.0% in the glimepiride, in the metformin and in the combined therapy groups, respectively (p < 0.001). The percentage of patients with decreased AIC of 7% or less was 18.9, 9.0 and 23.5% in the glimepiride, in the metformin and in the combined therapy groups, respectively (p = 0.01). The frequency of adverse events was similar for all the groups.\n The combined use of glimepiride plus metformin in a single presentation for 3 months showed to be efficacious and safe in patients with DM2 and secondary failure to glibenclamide.", "We investigated whether metformin hydrochloride has sustained beneficial metabolic and (cardio) vascular effects in patients with type 2 diabetes mellitus (DM2).\n We studied 390 patients treated with insulin in the outpatient clinics of 3 hospitals in a randomized, placebo-controlled trial with a follow-up period of 4.3 years. Either metformin hydrochloride, 850 mg, or placebo (1-3 times daily) was added to insulin therapy. The primary end point was an aggregate of microvascular and macrovascular morbidity and mortality. The secondary end points were microvascular and macrovascular morbidity and mortality, as separate aggregate scores. In addition, effects on hemoglobin A(1c) (HbA(1c)), insulin requirement, lipid levels, blood pressure, body weight, and body mass index were analyzed.\n Metformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001). Metformin was not associated with an improvement in the primary end point. It was, however, associated with an improvement in the secondary, macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P = .02), which was partly explained by the difference in weight. The number needed to treat to prevent 1 macrovascular end point was 16.1 (95% CI, 9.2-66.6).\n Metformin, added to insulin in patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve the primary end point. Metformin did, however, reduce the risk of macrovascular disease after a follow-up period of 4.3 years. These sustained beneficial effects support the policy to continue metformin treatment after the introduction of insulin in any patient with DM2, unless contraindicated. Trial Registration ClinicalTrials.gov Identifier: NCT00375388." ]

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[ "Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial.", "A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.", "Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice.", "Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.", "Randomized, controlled trial of amitriptyline versus placebo for adolescents with \"treatment-resistant\" major depression.", "A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression.", "[Lofepramine: a comparative clinical study with amitriptyline].", "A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression.", "A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder.", "A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression.", "Alprazolam and amitriptyline in the treatment of moderate depression.", "A controlled trial of maprotiline (Ludiomil) in depressed outpatients.", "Maprotiline-a double-blind study of a new tetracyclic antidepressant in severe depression.", "A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients.", "A double-blind study of minaprine versus amitriptyline in major depression.", "Placebo response rates in psychotic and nonpsychotic depression.", "A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.", "A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression.", "Symptom relief with amitriptyline in the irritable bowel syndrome.", "Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline.", "Paroxetine in the treatment of depression--a randomized comparison with amitriptyline.", "A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive disorders.", "A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients.", "Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients.", "Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.", "Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice.", "Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study.", "The comparative antidepressant value of lofepramine and amitriptyline. Results of a controlled trial with comments on the scales used.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients.", "A comparison of fluoxetine and amitriptyline in the treatment of major depression.", "A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients.", "Controlled trial of amitriptyline in general practice.", "Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study." ]

[ "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.", "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.", "Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.", "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.", "To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD).\n Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo.\n There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL.\n No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD.", "To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD).\n Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures.\n Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size.\n No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD.", "Lofepramine, a new tricycle antidepressant, is compared with amitriptyline in a double-blind study. A brief pharmacological description of the drug is made emphasizing its low toxicity and anticholinergic peripheral effects, high plasmatic concentration levels and good tolerance and elimination in comparison with some other known tricycle antidepressants. Sixty depressive outpatients of a Mental Health Service in Lima, 5 male and 55 female, aging 16 to 65, 29 endogenous and 31 neurotic were studied with both drugs in a equimolar dosage. Through the chi square test, no statistical significance was found in maximal therapeutic response, Hamilton Depression Rating Scale scores, type of depression, and side-effects xerostomy which is lesser with lofepramine. A discussion of these results is made and it is concluded that in the present study lofepramine compared with amitriptyline has a similar therapeutic effect. Though not statistically significant, lofepramine seems to be better for neurotic depression and patients sensitive to anticholinergic side-effects.", "A double-blind trial was undertaken to compare the antidepressant efficacy and the side effects of Lofepramine with those of Amitriptyline in the treatment of endogenous depression. The study involves 22 acutely ill endogenously depressive patients. 11 patients were treated with Lofepramine and the remaining 11 with Amitriptyline. The results demonstrate that both substances are effective in the treatment of depression. However, the therapeutical efficacy of Lofepramine is significantly greater than that of Amitriptyline. Furthermore, the tolerance of Lofepramine is better than that of Amitriptyline, and the side effects of Amitriptyline, especially in blood pressure dysregulation, are greater than those of Lofepramine.", "The efficacy and safety of fluoxetine, a new antidepressant agent, were assessed in a double-blind, parallel, randomized study of 44 outpatients with major depressive disorder. Following a 1-week placebo period, patients were randomly assigned to either fluoxetine or amitriptyline for a period of 5 weeks. The mean maintenance dosages were 55 mg/day for fluoxetine and 159 mg/day for amitriptyline. Both drugs were effective in relieving the symptoms of depression. The most frequently reported side effects were nausea and nervousness for fluoxetine, and dry mouth, dizziness, and drowsiness for amitriptyline.", "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.", "Forty-three out-patients with depression of a moderate degree were enrolled in a randomized, double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment. Patients were evaluated at the end of placebo washout and at Weeks 1, 2, 3 and 6 of drug therapy using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI). Drug dosage was determined in a fixed-flexible design resulting in mean final doses of alprazolam 3.2 mg/day and of amitriptyline 115 mg/day. Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D, BDI and HAM-A scales. Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group.", "A double blind comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline.", "A double-blind study was carried out comparing the antidepressant properties of maptotiline (a new tetracyclic antidepressant) and amitriptyline. Twenty-one hospitalized severely depressed patients, selected on the basis of clinical and psychometric criteria, completed the trial period of 28 days. The new drug was found to have an order of effectiveness similar to that of amitriptyline and both drugs were effective in agitated as well as retarded forms of depression. For both, the \"day of effect\", intended as the timing of sharp clinical improvement, tended to occur during the second week of treatment. Both drugs were well tolerated by most patients but one of the maprotiline patients presented a generalized rash which resolved after discontinuation of the drug. In conclusion, maprotiline is seen as an interesting addition to the group of major antidepressant drugs.", "The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle.", "This study was designed to compare the antidepressant effects of minaprine and amitriptyline in a group of 60 outpatients suffering from a major depressive episode as defined by the DSM III. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible daily doses of 200-300 mg of minaprine and 50-75 mg of amitriptyline. Both drugs showed significant global antidepressant efficacy with no significant difference between the two treatment groups. The Hamilton item 'psychomotor retardation' improved earlier with minaprine than amitriptyline. The incidence of anticholinergic adverse effects was significantly higher in the amitriptyline treatment group.", "The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline. Using a 14-day drug-free 'wash-out' period, they found that the placebo response rates were 0% for psychotic depressives and 13.3% for nonpsychotic depressives. Amitriptyline was significantly superior to placebo for both psychotic (P less than or equal to 0.05) and nonpsychotic (P less than or equal to 0.05) depressed patients.", "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.", "Background: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline-controlled, 5 week clinical study. Method: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score ≥ 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. Results: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. Conclusion: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated.", "Anti-depressants have been reported to be useful in the management of the Irritable Bowel syndrome. We studied the efficacy of amitriptyline for 12 weeks in a randomized double-blind placebo-controlled trial. Forty patients who met predefined criteria entered the trial. They received 25 mg amitriptyline for the first week, 50 mg for the second week and 75 mg nightly thereafter until the end of the 12th week. The drug and placebo groups were comparable in all major pretreatment variables. Amitriptyline was found to be significantly more effective than placebo in producing global improvement, increasing feelings of well-being, reducing abdominal pain and increasing satisfaction with bowel movements. Younger age and increasing extroversion predicted a better response to amitriptyline. Severity of depressive and anxiety symptoms and other personality variables did not influence outcome.", "The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group.", "Paroxetine is a new antidepressant drug with potent serotonin (5HT) uptake inhibitory properties. In this double-blind comparative study, the antidepressant effect of paroxetine and amitriptyline has been compared in 44 patients with depressive illnesses of an endogenous nature. Each drug was given for 6 weeks. The 17-item Hamilton Depression Scale was used to measure the antidepressant effect. Reported events were assessed applying a 22-item check list. Non-parametric statistical analyses were applied in the evaluation of treatment outcome for the 30 patients who completed the study. The results showed no significant differences in overall antidepressant efficacy between paroxetine and amitriptyline and that paroxetine displayed significantly fewer instances of dry mouth and orthostatic dizziness than amitriptyline. No obvious relationship was demonstrated between the plasma levels of the drugs and their clinical effects.", "1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Emergent Symptom Scale (TESS). 3 Mianserin and amitriptyline were comparable with respect to efficacy. 4 More adverse experiences were reported by amitriptyline patients. The predominant amitriptyline adverse experiences were of the anticholinergic type; the predominant mianserin adverse experience was drowsiness/fatigue. 5 The Efficacy Index (EI), a scale combining efficacy and adverse experiences, clearly demonstrated the superiority of mianserin over amitriptyline.", "As with other second-generation antidepressants, the antidepressive efficacy of mianserin was investigated in double-blind control group studies, mostly under outpatient conditions. This study tested the antidepressive efficacy and safety of mianserin as compared to amitriptyline in a sample of 51 depressed inpatients suffering from major depression. No statistically significant difference was found with regard to the main efficacy outcome criterion, the HAMD. The tolerability results demonstrated a superiority of mianserin with respect to vegetative symptoms and especially with respect to dryness of the mouth.", "The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.", "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 enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice.", "The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects.", "A double-blind controlled trial comparing the antidepressant activity of amitriptyline with lofepramine is reported. Forty-six patients entered the 4-week trial. Analysis of the Hamilton Depression Rating Scale scores at the beginning and end of the trial showed no significant difference between the therapeutic efficacy of lofepramine and amitriptyline. However, patients with endogenous depression responded significantly more rapidly to lofepramine as measured by Visual Analogue Scales and showed a significantly greater degree of clinical improvement after 4 weeks' treatment, as measured by Global Assessment. Adverse effects were similar in the two treatment groups. The use of rating scales in trials of depressive illnesses is discussed. The Visual Analogue Scale for depression was found to be a simple, useful and valid measure.", "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.", "Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors. The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine. However, most data were collected in samples of outpatients. To overcome this restriction, a six-week double-blind control-group study, comparing 30 mg paroxetine with 150 mg amitriptyline per day, was performed in a sample of inpatients suffering from major depression. Generally speaking, the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline, either with respect to the total score on the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions or with respect to the subscores of the HAMD. One exception was the retardation subscore, in which amitriptyline showed a greater degree of reduction. Both drugs had a characteristic side-effect profile. Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea.", "Fluoxetine, a new serotonin uptake blocking antidepressant, was compared with amitriptyline in a double-blind study. Patients were diagnosed as having major depression, according to DSM-III criteria, when interviewed with the Diagnostic Interview Schedule. There was significant improvement in patient and observer ratings of depression in both groups, with no difference between groups. Recent memory improved significantly in the fluoxetine group but not in the amitriptyline group. Numbers of patients reporting side-effects were similar but the profiles of side-effects were different, with more patients on amitriptyline reporting anticholinergic and intolerable side-effects.", "A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.", "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.", "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." ]

[ "15499601", "11843249" ]

[ "Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer.", "Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer." ]

[ "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.", "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." ]

[ "20375190", "12052800", "15158629" ]

[ "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.", "Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum.", "Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial." ]

[ "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.", "To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia.\n Double masked, randomised placebo controlled trial.\n A slum community in New Delhi, India.\n 2482 children aged 6 to 30 months.\n Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for four months. Both groups received single massive dose of vitamin A (100 000 IU for infants and 200 000 IU for older children) at enrollment.\n All households were visited weekly. Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians.\n At four months the mean plasma zinc concentration was higher in the zinc group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups (absolute risk reduction -0.2%, 95% confidence interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval 0.4% to 4.6%). After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74, 95% confidence interval 0.56 to 0.99.\n Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin A.", "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." ]

[ "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." ]

[ "15184205", "8296253", "7842191", "11405516", "9476870", "2148702", "17603828", "14514935", "8609098", "12324673", "9281927", "7570406", "11001084", "18302840" ]

[ "Peak flow monitoring for guided self-management in childhood asthma: a randomized controlled trial.", "Controlled trial evaluation of an asthma education programme for adults.", "Asthma self-management education program by home monitoring of peak expiratory flow.", "Benefit from the inclusion of self-treatment guidelines to a self-management programme for adults with asthma.", "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.", "An internet-based interactive telemonitoring system for improving childhood asthma outcomes in Taiwan.", "Can a self-management programme delivered by a community pharmacist improve asthma control? A randomised trial.", "Evaluation of individualized asthma self-management programs.", "A randomised trial of self-management planning for adult patients admitted to hospital with acute asthma.", "An evaluation of a self-management program for adults with asthma.", "Randomised trial of an asthma self-management programme for adults.", "A randomized controlled evaluation of specialist nurse education following accident and emergency department attendance for acute asthma.", "Pharmaceutical care for asthma patients: a community pharmacy-based pilot project." ]

[ "We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma. In an open-randomized, parallel-group, controlled trial, we studied children aged 7-14 years with moderate asthma. After a 4-week run-in, 90 children were randomized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks. Thresholds for action based on PEF were 70% of best (for increasing inhaled steroids) and 50% of best (for commencing prednisolone). Children were asked to perform twice-daily spirometry at home (using an electronic recording spirometer that revealed only PEF to the study group alone) and to record a symptom diary. The mean daily symptom score was the main outcome. There were no differences between groups in mean symptom score or in spirometric lung function, PEF, quality of life score, or reported use of health services over 12 weeks. During acute episodes, children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70% of best so that overall PEF did not contribute to this important self-management decision. Knowledge of PEF did not enhance self-management even during acute exacerbations.", "To improve asthma control and reduce readmission rates through increased knowledge and the development of self management skills, a brief (three hour) adult education programme was developed.\n The course was designed to improve inhaler skills and to teach how to adjust drug doses according to peak flow (PEF) measurements and a treatment plan. It was evaluated in a randomised controlled trial in 76 patients admitted to hospital for asthma by using questionnaires, spirometry, and home monitoring of PEF at entry and at five and 10 months after intervention. The questionnaire provided measures of knowledge about asthma, self management behaviour appropriate to asthma control, asthma symptom frequency and severity, and psychosocial disturbance attributable to asthma.\n During the 10 months observation period the readmission rate for the educated group was one seventh that of the control group and attendance at accident and emergency departments also decreased. No consistent differential improvements were observed in spirometric results, average PEF, or mean daily variability of PEF. Both groups showed improvements in measures of asthma knowledge, behaviour, symptoms, and psychosocial disturbances. However, the intervention group showed a significantly greater improvement in some measures of asthma knowledge and self management skills.\n Despite minimal effect on measures of airway function, substantial changes in illness behaviour and use of health care facilities can be achieved by a brief asthma education programme.", "A prospective controlled trial of home monitoring of peak expiratory flow rate (PEFR) was conducted to determine the usefulness of an objective measure of lung function in association with an education program and a medication self-management plan in reducing morbidity in adult patients with asthma. Thirty-five patients managed themselves, using peak flow readings as the basis for the therapeutic plan coupled with educational intervention, whereas 35 control patients used symptoms and spirometric data for following physicians' treatment plans. After a 6-mo study period, patients in the experimental group showed statistically significant improvements in morbidity parameters (days lost from work, acute asthma attacks, days on antibiotic therapy, physician consultations, and emergency room admissions for asthma), increases in FVC, FEV1, and FEV1/FVC, mean PEFR and mean morning PEFR, decrease in percentage of the mean PEFR amplitude, and a reduction in the use of inhaled beta-agonists, oral theophylline, and oral prednisone. Although improvements in some of these parameters were also found in the control group, they did not reach the levels of significance obtained in the experimental group. The personal use of an objective measure of lung function in association with a medication self-management plan leads to improvement in the patient's condition.", "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.", "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.", "A randomized, controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids, an Internet-based interactive asthma educational and monitoring program, used in the management of asthmatic children. One hundred sixty-four (n = 164) pediatric patients with persistent asthma were enrolled and randomized into two study groups for a 12-week controlled trial. The intervention group had 88 participants who were taught to monitor their peak expiratory flows (PEF) and asthma symptoms daily on the Internet. They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program. The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management. Disease control was assessed by weekly averaged PEF values, symptom scores, and asthma control tests. Adherence measures were assessed by therapeutic and diagnostic monitoring. Outcome was assessed by examining quality of life and retention of asthma knowledge. The data were analyzed by comparing results before and after the trial. At the end of trial, the intervention group decreased nighttime (-0.08 +/- 0.33 vs. 0.00 +/- 0.20, p = 0.028) and daytime symptoms (-0.08 +/- 0.33 vs. 0.01 +/- 0.18, p =0.009); improved morning (241.9 +/- 81.4 vs. 223.1 +/- 55.5, p =0.017) and night PEF (255.6 +/- 86.7 vs. 232.5 +/- 55.3, p =0.010); increased adherence rates (p < 0.05); improved well-controlled rates (70.4% vs. 55.3%, p < 0.05); improved knowledge regarding self-management (93.2% vs. 70.3%, p < 0.05); and improved quality of life (6.5 +/- 0.5 vs. 4.3 +/- 1.2 on a 7-point scale, p < 0.05) when compared with conventional management. The Internet-based asthma telemonitoring program increases selfmanagement skills, improves asthma outcomes, and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers.", "No randomised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists. Most randomised trials of asthma self-management have recruited participants from secondary care; there is uncertainty regarding its effectiveness in primary care. A randomised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy.\n Twenty four adults attending a community pharmacy in Tower Hamlets, east London for routine asthma medication were randomised into two groups: the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist. Participants self-completed the North of England asthma symptom scale at baseline and 3 months later.\n The groups were well matched at baseline for demographic characteristics and mean (SD) symptom scores (26.3 (4.8) and 27.8 (3.7) in the intervention and control groups, respectively). Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 (4.2) and 28.1 (3.5), respectively (p<0.001; difference adjusted for baseline scores=7.0 (95% CI 4.4 to 9.5).\n A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy. Further studies should attempt to confirm these findings using larger samples and a wider range of outcome measures.", "We compared the effectiveness of personalized asthma self-management recommendations with that of a group self-management program. We assigned each of 34 asthma patients randomly to one of three conditions: individualized asthma self-management, group asthma self-management, and control. We derived individualized self-management recommendations from patient recordings of asthma occurrence, asthma precipitants, and peak expiratory flow rate made during a 3-month period. The group program we used was the Wheezers Anonymous program. As compared to a control group of patients who received no self-management training, the patients in both the individualized and group condition evidenced improvement of pulmonary function, as measured daily with a home peak flow meter. The improvement was equivalent for patients in the two conditions. Patients in the individualized condition also exhibited a drop in frequency of asthma attacks, but patients in the group condition did not. We concluded that individualized asthma self-management is effective in reducing symptoms of asthma.", "There is still debate over the benefit of self-management programmes for adults with asthma. A brief self-management programme given during a hospital admission for acute asthma was tested to determine whether it would reduce readmission.\n A randomised controlled trial was performed in 280 adult patients with acute asthma admitted over 29 months. Patients on the self-management programme (SMP) received 40-60 minutes of education supporting a written self-management plan. Control patients received standard care (SC).\n One month after discharge SMP patients were more likely than SC patients to report no daytime wheeze (OR 2.6, 95% CI 1.5 to 5.3), no night disturbance (OR 2.0, 95% CI 1.2 to 3.5), and no activity limitation (OR 1.5, 95% CI 0.9 to 2.7). Over 12 months 17% of SMP patients were re-admitted compared with 27% of SC patients (OR 0.5, 95% CI 0.3 to 1.0). Among first admission patients, OR readmission (SMP v SC) was 0.2 (95% CI 0.1 to 0.7), p<0.01. For patients with a previous admission, OR readmission was 0.8 (95% CI 0.4 to 1.6), p=0.6. SMP patients were more likely than SC patients to be prescribed inhaled steroids at discharge (99% v 92%, p=0.03), oral steroids (98% v 90%, p=0.06), and to have hospital follow up (98% v 84%, p<0.01) but adjustment for these differences did not diminish the effect of the self-management programme.\n A brief self-management programme during hospital admission reduced post discharge morbidity and readmission for adult asthma patients. The benefit of the programme may have been greater for patients admitted for the first time. The programme also had a small but significant effect on medical management at discharge.", "The purpose of this study was to evaluate the impact of a self-management program for adults with moderate to severe asthma on compliance with inhaled, prescribed, nonemergency medications; asthma symptoms; and airway obstruction. In this controlled experimental study, 55 subjects from a rural community were randomized to one of two groups. Self-efficacy theory served as the framework for this study. Primary measures included the Metered Dose Inhaler (MDI) Chronolog, a journal of daily asthma concerns, and a peak-flow meter to appraise airway obstruction. Secondary measures included the Asthma Self-Management Assessment Tool (ASMAT) and the Self-Efficacy for Asthma Management Scale (SEAMS). These measures were completed pre- and post-intervention. Data analysis using descriptive and inferential statistics revealed that subjects receiving the self-management program increased compliance with inhaled medications (U = 271, p = .043).", "A hospital based, community service asthma education programme for adults to improve asthma knowledge, promote compliance with medication, and reduce morbidity was evaluated.\n The programme was evaluated using a randomised experimental and control group design with repeated measurements over 12 months. A volunteer community sample of 192 respondents was recruited of whom 116 satisfied the inclusion criteria. At the 12 month follow up some data were obtained for all subjects. Intervention subjects attended four 2.5 hour education sessions at weekly intervals. An asthma knowledge questionnaire was administered and compliance was assessed from diary records. Morbidity was assessed retrospectively by questionnaire, prospectively by diary, and objectively by spirometry and serial peak expiratory flow rate monitoring. The adequacy of medical treatment was also assessed. Data were collected at baseline, immediately after the intervention, and at three, six, nine, and 12 months after intervention.\n Improvements occurred in knowledge and compliance in the intervention group but the impact on morbidity was modest; this was due, at least in part, to the inadequacy of medical treatment.\n Treatment of asthma should be reviewed and optimised in conjunction with self-management programmes in order to improve health outcomes.", "We investigated whether hospital-based specialist asthma nurses improved recognition and self-treatment of asthma episodes by patients followed up after attending accident and emergency departments (A&E) for asthma exacerbations. We carried out a randomized prospective controlled trial of adult asthma self-management, following a hospital outpatient nurse consultation in two outer-London District General Hospitals (secondary care centres). The study included 211 adults, over 18 years old (mean age 40 years) who attended for asthma in two accident and emergency departments over 13 months. One hundred and eight evaluable patients were randomized into the control group who continued with their usual medical treatment and were not offered any intervention during the study period. One hundred and three evaluable patients were randomized into the intervention group. They were offered three 6-weekly outpatient appointments with one of two specialist asthma nurses for a structured asthma consultation, after attendance at the accident and emergency department. Following assessment of their asthma treatment and control, the nurses advised patients, through the use of self-management-plans, how to recognize and manage uncontrolled asthma and when to seek medical assistance. Medication and inhaler device type were altered if necessary The primary outcome was patient reported self-management of asthma exacerbations for 6 months. Secondary outcomes were assessed at baseline, 3 months and 6 months. These included home peak flow and symptom diaries, structured telephone questionnaires and audit of general practitioner records to determine utilization of services (6 months before and after A&E). Data were analysed on an intention to treat basis by multiple and logistic regression. The intervention group increased their use of inhaled topical steroids in 31/61 (51%) vs. 15/70 (21%) attacks in controls (OR 3.91 CI 1.8-8.4, P<0.001) and their use of rescue medication in 54/61 (89%) severe attacks vs. 53/70 (76%) controls (OR 2.88 CI 1.1-7.9, P<0.05). Intervention patients had significantly higher (mean 20.1 l min(-1); CI 0.4-39.7; P<0.05) and less variable PEF and significantly lower and less variable symptom scores 6 months after entry. Thirty-four percent of intervention patients vs. 42% controls had severe attacks (61 and 70 respectively, OR 0.96 CI 0.7-1.4) during the 6 months. Intervention patients had fewer days off work than controls in the first 3 months (NS) but similar days off during the 6-month period. Intervention patients had fewer episodes away from work in the first (0.34 vs. 0.54, P = 0.08) and the second 3 months (0.25 vs. 0.30, NS) than the controls. Over 80% of the patients records were audited by their general practitioners; the active group had less routine consultations with the doctor (P = 0.03) and practice nurse (P = 0.03), less consultations for uncontrolled episodes (P = 0.06) and less hospital visits (NS) than the controls. Hospital-based specialist nurses reduced asthma morbidity by improving patient self-management behaviour in acute attacks leading to reduced symptoms, improved lung function, less time off work and fewer consultations with health professionals.", "Asthma is a clinical problem with social, psychological, and economic burdens. To improve patient disease management and quality of life (QOL), different education programs have been developed. The purpose of this study is to adapt and implement a community-based educational program for patients with asthma. A prospective, randomized, controlled trial was performed. Fifty individuals with mild asthma (aged 18-40 years) that have been attending pharmacies were included in the sample. The duration of the disease was 9 +/- 4.21 years. A 4-month study was conducted on essence of asthma and factors that can intensify it; nourishing facts, allergens, and physical activities; self-management and use of tobacco; and pharmacotherapy, inhalation technique, and possible adverse drug reactions. Patient's health-related QOL was assessed in the beginning and at the end of the survey. Parameters assessed during the four stages of the program were patients' peak expiratory flow (PEF); inhaler technique; severe asthma symptoms, including breathlessness, hospitalization rates, frequency of urgent medical aid calls, and frequency of general practitioner visits; compliance with therapy; and satisfaction with pharmacy services. Health-related QOL of the intervention patients was improved at 4 months and there was improvement in the PEF rate, decrease in patients' breathlessness and wheezing rate, decrease in the reported hospitalizations rate because of the disease, decrease in the physician's visits, and increase in satisfaction with pharmacist-provided information. The positive results from the educational approach show a potential to decrease asthma disease complications and show a positive impact on patients' inhaler technique, patients' opinions about the pharmacy services, and information obtained." ]

[ "9228354", "10027430", "9850359", "3282826", "2669554", "8323451", "10983616", "2844548", "2236929", "12475833", "9828851", "7913155", "17254760" ]

[ "A comparison of double-strength beclomethasone dipropionate (84 microg) MDI with beclomethasone dipropionate (42 microg) MDI in the treatment of asthma.", "Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma.", "Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.", "Six-month double-blind, controlled trial of high dose, concentrated beclomethasone dipropionate in the treatment of severe chronic asthma.", "Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.", "[Effects of high doses of beclomethasone dipropionate in bronchial asthma].", "Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group.", "Effects of inhaled beclomethasone dipropionate on beta 2-receptor function in the airways and adrenal responsiveness in bronchial asthma.", "Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma.", "Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma: a 12-week, randomized, double-blind, placebo-controlled study.", "Fluticasone propionate 750 micrograms/day versus beclomethasone dipropionate 1500 micrograms/day: comparison of efficacy and adrenal function in paediatric asthma.", "Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group.", "Beclometasone dipropionate extrafine aerosol versus fluticasone propionate in children with 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.", "The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis.\n A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy (inhaled beta-agonist and CFC-BDP [< or = 400 microg/d]). A short course of oral prednisone, 30 mg/d for 7 to 12 days, was followed to establish the patients were steroid responsive and to provide an \"in-study\" baseline of \"optimal\" asthma control.\n A total of 347 patients were then randomized to HFA-BDP 400 microg/d, CFC-BDP 800 microg/d, or HFA-placebo for 12 weeks.\n Morning peak expiratory flow (AM PEF) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment. All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo. The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported.\n These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied, but at half the total daily dose.", "Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.", "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 dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.", "To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.", "The objective of this study was to evaluate the efficacy and safety of low doses (50 and 100 microg b.i.d.) of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) extrafine aerosol in improving asthma control. Reformulation of BDP in a new chlorofluorocarbon (CFC)-free propellant (HFA) has produced an extrafine aerosol with increased delivery of the drug to the airways of the lung. The study population comprised 270 steroid-naive patients with mild to moderate asthma (mean baseline forced expiratory volume in 1 sec [FEV1] as a percentage of predicted normal of 65%-85%). This was a 6-week, blinded, placebo-controlled, multicenter study. Patients were randomized to receive 50 or 100 microg b.i.d. HFA-BDP or HFA-placebo. Treatment with either 50 or 100 microg b.i.d. HFA-BDP resulted in a significantly greater improvement compared with placebo in FEV1 (mean change from baseline as percentage of predicted normal of 6.7%, 8.6%, and 0.4%, respectively; p < or = 0.01 active treatment groups vs. placebo), with a significant trend toward increasing improvement with increasing doses (p < or = 0.0001). Treatment also resulted in significantly greater mean changes from baseline in morning peak expiratory flow compared with placebo (29.5, 33.8, and 5.0 L/min, respectively; p < or = 0.01 active treatment groups vs. placebo). All other pulmonary function and asthma symptom measures supported these data. The study treatments were well tolerated. These results show that low doses of HFA-BDP extrafine aerosol effectively improve asthma control in adult patients with mild to moderate asthma. However, it is important that inhaled corticosteroid therapy is still given at a dose high enough to control airway inflammation as well as asthma symptoms.", "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.", "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.", "Beclomethasone dipropionate (BDP) has been formulated as an extrafine aerosol (hydrofluoroalkane-134a [HFA]-BDP) [QVAR; 3M Pharmaceuticals; St Paul, MN], which gives improved lung deposition compared with chlorofluorocarbon (CFC)-BDP. The clinical efficacy of HFA-BDP has been established in adult asthma at a required dose below that of CFC-BDP, but has not been evaluated in children.\n To examine the efficacy and safety of HFA-BDP in childhood asthma.\n A 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study involving 353 children aged 5 to 12 years with moderate, symptomatic asthma. After a 2-week run-in period, patients were randomized to HFA-BDP, 80 micro g/d (n = 120); HFA-BDP, 160 micro g/d (n = 117); or HFA-placebo (n = 116) administered twice daily.\n Hospital outpatient.\n HFA-BDP, 80 micro g/d and 160 micro g/d, produced a significant, dose-related increase from baseline in FEV(1) percent predicted compared with placebo. At week 12, mean changes from baseline in FEV(1) percent predicted were 9.2% (p < or = 0.01 vs placebo), 10% (p < or = 0.01 vs placebo), and 3.9% for the HFA-BDP 80 micro g/d, HFA-BDP 160 micro g/d, and placebo groups, respectively. There was also a significant decrease in daily beta-agonist use, improvement in peak expiratory flow, and increase [correction] in the percentage of days free from asthma symptoms (p < or = 0.05 for HFA-BDP, 160 micro g/d, vs placebo at weeks 11 to 12). HFA-BDP was well tolerated, with no significant differences in the incidence or nature of adverse events between HFA-BDP and placebo groups. Neither were there significant differences between groups in mean percentage change from baseline in the morning plasma cortisol level at week 12 or in the percentage of patients with morning plasma cortisol levels below the reference range at baseline and week 12. In a subgroup tested, the percentage of patients with an abnormal response to low-dose adrenocorticotropic hormone stimulation at week 12 was low and similar among all groups.\n HFA-BDP, 80 to 160 micro g/d, is effective and safe in childhood asthma.", "Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.\n The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.\n There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.\n FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.", "Guidelines on asthma management recommend that in patients who still have symptoms on treatment with low-dose inhaled corticosteroids the first step should be an increase in inhaled corticosteroid dose. The addition of long-acting inhaled beta 2-adrenoceptor agonists is another option. We have compared these two strategies in a randomised, double-blind, parallel-group trial. We studied 429 adult asthmatic patients who still had symptoms despite maintenance treatment with 200 micrograms twice daily inhaled beclomethasone dipropionate (BDP). 3 did not provide verifiable data. Of the others, 220 were assigned salmeterol xinafoate (50 micrograms twice daily) plus BDP and 206 were assigned higher-dose BDP (500 micrograms twice daily) for 6 months. The mean morning peak expiratory flow increased from baseline in both groups, but the increase was greater in the salmeterol/BDP group than in the higher-dose BDP group at all time points (differences 16-21 L/min, p < 0.05). Mean evening PEF also increased with salmeterol/BDP but not with higher-dose BDP. There were significant differences in favour of salmeterol/BDP in diurnal variation of PEF (all time points) and in use of rescue bronchodilator (salbutamol) and daytime and night-time symptoms (some time points). There was no significant difference between the groups in adverse effects or exacerbations of asthma, indicating that in this group of patients regular beta 2-agonist therapy was not associated with any risk of deteriorating asthma control over 6 months. This study suggests a need for a flexible approach to asthma management.", "Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose." ]

[ "17436825", "1981436", "138560", "9649660", "6216858", "11586012", "17436826", "21269305", "12695127", "2530191", "16702498", "150346", "11867968", "11701404", "131678", "3157706", "2965628", "15588555", "14988688", "2938993", "2943311" ]

[ "Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris.", "A double-blind comparison of topical clindamycin and oral minocycline in the treatment of acne vulgaris.", "Minocycline therapy in acne vulgaris.", "A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris.", "Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris.", "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.", "Safety and efficacy of a new extended-release formulation of minocycline.", "Efficacy of oral antibiotics on acne vulgaris and their effects on quality of life: a multicenter randomized controlled trial using minocycline, roxithromycin and faropenem.", "Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline.", "[Treatment of acne vulgaris. A comparison of doxycycline versus minocycline].", "Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study.", "Minocycline versus doxycycline in the treatment of acne vulgaris. A double-blind study.", "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.", "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.", "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.", "A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris.", "Isotretinoin versus minocycline in cystic acne: a study of lipid metabolism.", "Oral spironolactone: an effective treatment for acne vulgaris in women." ]

[ "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.", "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 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.", "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.", "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.", "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", "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.", "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.", "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.", "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.", "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.", "nan", "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.", "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%).", "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).", "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.", "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.", "The effect of oral spironolactone (200 mg daily) on acne vulgaris has been studied in 21 women in a randomized, placebo-controlled, double-blind crossover study using 3 month treatment periods. Compared with placebo, spironolactone produced significant improvement as assessed by subjective benefit (P less than 0. 001), number of inflamed lesions (P less than 0 . 001) and by an independently evaluated photographic method (P less than 0 .02). There was a fall in sex hormone binding globulin but no significant changes in plasma testosterone and derived free testosterone. Initial plasma androgen levels were no higher in responders than in non-responders, nor did oral contraceptive use appear to affect clinical response. Spironolactone is a useful alternative therapy for women with acne vulgaris." ]

[ "14770380", "10434220", "11984383", "9378876", "17304779", "19731848", "12657991" ]

[ "Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea.", "An alternative method to alleviate postoperative nausea and vomiting in children.", "Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting.", "Peppermint oil: a treatment for 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 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.", "Randomized, double-blinded comparison of tropisetron and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "This prospective, randomized, placebo-controlled, double-blinded study was designed to evaluate the efficacy of tropisetron in preventing postoperative nausea and vomiting after elective supratentorial craniotomy in adult patients. We studied 65 ASA physical status I-III patients aged 18 to 76 years who were undergoing elective craniotomy for resection of various supratentorial tumors. Patients were divided into two groups and received either 2 mg of tropisetron (group T) or saline placebo (group P) intravenously at the time of dural closure. A standard general anesthetic technique was used. Episodes of nausea and vomiting and the need for rescue antiemetic medication were recorded during 24 hours postoperatively. Demographic data, duration of surgery and anesthesia, and sedation scores were comparable in both groups. Nausea occurred in 30% of group T patients and in 46.7% of group P patients (P >.05). The incidence of emetic episodes was 26.7% and 56.7% in the two groups (P <.05). Rescue antiemetic medication was needed in 26.7% and 60% of the patients (P <.05). Administration of a single dose of tropisetron (2 mg intravenously) given at the time of dural closure was effective in reducing postoperative nausea and vomiting after elective craniotomy for supratentorial tumor resection in adult patients." ]

[ "21149743", "21636633", "19418107", "15749130", "10564627", "10632830", "9734786", "18573775", "18308500", "12244644", "8327418", "12781927", "16720537", "11958495", "17954796", "14528540", "15006907", "19105686", "17627015", "17689600", "12883063", "8302104", "10358689", "7707420", "17389293", "16377602", "20157016", "1571644", "15782876", "15249521", "11085838", "2764657", "8719151", "12590989", "20978060", "12464832", "17196358", "16377604", "15150305", "8552852" ]

[ "Electronic patient messages to promote colorectal cancer screening: a randomized controlled trial.", "Effect of evidence based risk information on \"informed choice\" in colorectal cancer screening: randomised controlled trial.", "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.", "Tailored risk notification for women with a family history of breast cancer.", "Does informed consent alter elderly patients' preferences for colorectal cancer screening? Results of a randomized trial.", "Using an office system intervention to increase breast cancer screening.", "Randomized trial of a self-administered decision aid for colorectal cancer screening.", "A randomized trial of two print interventions to increase colon cancer screening among first-degree relatives.", "Message framing and mammography screening: a theory-driven intervention.", "A randomized trial of the impact of risk assessment and feedback on participation in mammography screening.", "Tailored messages for breast and cervical cancer screening of low-income and minority women using medical records data.", "Effects of communicating social comparison information on risk perceptions for colorectal cancer.", "Randomized controlled trial of a patient decision aid for colorectal cancer screening.", "Informed choice in mammography screening: a randomized trial of a decision aid for 70-year-old women.", "The impact of tailored interventions on a community health center population.", "A large population-based randomized controlled trial to increase attendance at screening for cervical cancer.", "Mammography screening after risk-tailored messages: the women improving screening through education and risk assessment (WISER) randomized, controlled trial.", "Effects of colon cancer risk counseling for first-degree relatives.", "Preference-based electronic decision aid to promote colorectal cancer screening: results of a randomized controlled trial.", "Randomised controlled trial of the effect of evidence based information on women's willingness to participate in cervical cancer screening.", "Strategies to increase mammography utilization.", "A randomized trial of breast cancer risk counseling: the impact on self-reported mammography use.", "Effects of individualized breast cancer risk counseling: a randomized trial.", "Web-based proactive system to improve breast cancer screening: a randomized controlled trial.", "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.", "Effects of a mail and telephone intervention on breast health behaviors.", "Cancer: improving early detection and prevention. A community practice randomised trial.", "Reconciling population benefits and women's individual autonomy in mammographic screening: in-depth interviews to explore women's views about 'informed choice'.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Videotape-based decision aid for colon cancer screening. A randomized, controlled trial.", "Promoting cancer screening. A randomized, controlled trial of three interventions.", "A randomised controlled trial of strategies to prompt attendance for a Pap smear.", "Comparison of tailored interventions to increase mammography screening in nonadherent older women.", "A decision aid to support informed choices about bowel cancer screening among adults with low education: randomised controlled trial.", "Feasibility of using a computer-assisted intervention to enhance the way women with breast cancer communicate with their physicians.", "The effect of telephone versus print tailoring for mammography adherence.", "Facilitating informed decision making about breast cancer risk and genetic counseling among women calling the NCI's Cancer Information Service.", "A randomized trial of direct mailing of fecal occult blood tests to increase colorectal cancer screening.", "Education program for general practitioners on breast and cervical cancer screening: a randomized trial. PRE.SA.GF Collaborative Group." ]

[ "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.", "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.", "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.", "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.", "To assess the impact of informed consent on elderly patients' colorectal cancer (CRC) screening preferences.\n Randomized, controlled trial.\n Four general internal medicine practices.\n We studied 399 elderly patients visiting their primary care provider for routine office visits.\n Patients were randomized to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening. One intervention described CRC mortality risk reduction in relative terms; the other, in absolute terms.\n The main outcome measure was intent to begin or continue fecal occult blood testing (FOBT), flexible sigmoidoscopy, or both. There was no difference in screening interest between the control group and the two information groups (p =.8). The majority (63%) of patients intended to begin or continue CRC screening. Informed patients were able to gauge more accurately the positive predictive value of screening (p =.0009). Control patients rated the efficacy of screening higher than did patients receiving relative risk reduction information, who rated it higher than did patients receiving absolute risk reduction information (p =.0002).\n Elderly patients appeared to understand CRC screening information and use it to gauge the efficacy of screening, but provision of information had no impact on their preferences for screening. In view of the large proportion who preferred not to be screened, we conclude that elderly patients should be involved in the screening decision. However, factors other than provision of information must determine their CRC screening preferences.", "To evaluate an innovative approach to continuing medical education, an outreach intervention designed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practices.\n Randomized, controlled trial with primary care practices assigned to either the intervention group or control group, with the practice as the unit of analysis.\n Twenty mostly rural counties in North Carolina.\n Physicians and staff of 62 randomly selected family medicine and general internal medicine practices, primarily fee-for-service, half group practices and half solo practitioners.\n Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance, and to assist these primary care practices in developing office systems tailored to increase breast cancer screening.\n Physician questionnaires were obtained at baseline and follow-up to assess the presence of five indicators of an office system. Three of the five indicators of office systems increased significantly more in intervention practices than in control practices, but the mean number of indicators in intervention practices at followup was only 2.8 out of 5. Cross-sectional reviews of randomly chosen medical records of eligible women patients aged 50 years and over were done at baseline (n = 2,887) and follow-up (n = 2,874) to determine whether clinical breast examinations and mammography, were performed. Results for mammography were recorded in two ways, mention of the test in the visit note and actual report of the test in the medical record. These reviews showed an increase from 39% to 51% in mention of mammography in intervention practices, compared with an increase from 41% to 44% in control practices (p = .01). There was no significant difference, however, between the two groups in change in mammograms reported (intervention group increased from 28% to 32.7%; control group increased from 30.6% to 34.0%, p = .56). There was a nonsignificant trend (p = .06) toward a greater increase in performance of clinical breast examination in intervention versus control practices.\n A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography, but had little impact on actual performance of breast cancer screening. At follow-up, few practices had a complete office system for breast cancer screening. Outreach approaches to assist primary care practices implement office systems are promising but need further development.", "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.", "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.", "Although the rising incidence of breast cancer has prompted a surge of intervention strategies aimed at increasing women's use of mammography screening, the majority of patient-directed interventions have not been driven by relevant theoretical work on persuasive health communication. The authors evaluated an intervention derived from prospect theory that was designed to increase women's adherence to recommendations for annual mammography screening. They sent 1 of 3 reminder letters (positive frame, negative frame, or standard hospital prompt) to 929 randomly selected women who were due for mammography screening and had been identified as having either a positive or negative family history of breast cancer. The primary hypothesis that women with a positive history would be more responsive to negatively framed messages, whereas women with a negative history would be more responsive to positively framed letters, was not confirmed. The lack of support for predictions derived from prospect theory raises important questions about the generalizability of laboratory research to natural settings.", "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.", "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.", "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.", "To conduct a pilot test of a decision aid designed to help patients choose among currently recommended colorectal cancer screening programs.\n Randomized controlled trial comparing a patient decision aid based on multicriteria decision-making theory with a simple educational intervention.\n 96 patients at average risk for colorectal cancer seen in an Internal Medicine practice in Rochester, New York.\n The two primary outcome measures were patient decision process and the decision outcome. Patient decision process was assessed using the decisional conflict scale. Decision outcome was defined as the proportion of colorectal cancer screening plans carried out.\n After controlling for the effects of the physicians in a factorial analysis of variance, patients who used the decision aid had lower decisional conflict regarding colorectal cancer screening decisions (F ratio 6.47, P = 0.01) due to increased knowledge, better clarity of values, and higher ratings of the quality of the decisions they made. There was no difference between the groups in decision outcomes: 52% of patients in the control group and 49% in the experimental group completed planned screening tests (P = 1.0).\n In a pilot study, a multicriteria-based patient decision aid for colorectal cancer screening improved patients' decision-making processes but had no effect on the implementation of screening plans.", "Many women who have participated in mammography screening are now approaching 70 years of age. These women are advised to consider both the benefits and harms of continuing to be screened. Doing so may be difficult for individual women, and there are no evaluated decision support tools to assist them.\n To assess the effect of a decision aid (DA) about whether to continue or stop mammography screening for women aged 70 years, a population-based, randomized controlled trial was conducted in New South Wales, Australia. Women aged 70 years who had regularly participated in mammography screening were eligible to participate in the trial. Women received a DA providing balanced, quantitative information or standard information available from the screening program. The main outcomes were the percentage of women making an informed choice about whether to continue or stop screening and the percentage of women participating in the screening.\n Women who received the DA (the intervention group) were better informed than the control group (mean increase in knowledge score out of 10, 2.62 for the intervention group vs 0.68 for the control group; P < .001), and a significantly greater percentage made an informed choice (73.5% vs 48.8%; P < .001). The DA did not increase anxiety and slightly reduced decisional conflict. There was no difference in the percentage of women who participated in screening within 1 month.\n This DA increased knowledge and assisted women to make an informed choice. It did not alter participation in screening. The DA is an effective way to assist women to make a decision about continuing mammography screening and seems to be a feasible intervention within a population screening program.", "We conducted a 4-year randomized study in a community health center that serves primarily low income Blacks in Durham, North Carolina. Patients (1318 at baseline) were assigned randomly to one of three study groups: provider prompting intervention alone, provider prompting and tailored print materials or the previous group and tailored telephone counseling. The purpose of the study was to determine whether increasingly intensive, tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms, Pap tests and overall cancer screening compliance. Thus, the combination of tailored print interventions (print and telephone) should have been more effective than the provider prompting intervention alone, or the print intervention and prompting combination. This is one of the few studies to examine a measure of overall cancer screening compliance and to assess the benefit of combinations of tailored interventions in promoting adherence to cancer screening. Patients gave extremely high ratings to the interventions. At the bivariate level, we found a significant effect of the most intensive group (provider prompting intervention, tailored print communications and tailored telephone counseling) on Pap test compliance (P = 0.05) and borderline significance at the multivariate level (P = 0.06) as well on overall screening compliance (P = 0.06). There was not a significant effect on mammography, probably because a majority of the patients were receiving regular mammograms. We also found some important subgroup differences. For example, a larger proportion of women reported Pap tests in the tailored print and counseling group when they believed the materials were 'meant for me.' These results show that a combination of tailored interventions may have potential for reaching the women who have too often been labeled the 'hard to reach.'", "Although cervical cancer is one of the potentially most preventable malignancies, it is still fairly common. In settings with established screening programs, increased compliance is important for future reduction in cervical cancer incidence, but it is presently unclear how this can be effectively achieved.\n We conducted a randomized controlled trial including all 12,240 women invited to organized screening in Sweden. To increase compliance, three successive interventions were tested: (a) modified invitation versus the standard invitation letter, (b) reminder letter to nonattenders after the first intervention versus no reminder letter, and (c) phone reminder to nonattenders after the reminder letter versus no phone reminder. We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities.\n The modified invitation did not increase attendance compared with the standard invitation letter [difference 1.3% 95% confidence interval (CI) -0.3 to 2.9]. In contrast, a reminder letter increased the proportion of women attending with 9.2% (95% CI 7.9-10.5) compared with women who did not receive a reminder letter, and a phone reminder increased the proportion of women attending with 31.4% (95% CI 26.9-35.9). Combinations of modified invitation, written reminder, and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled.\n Simple reminders by mail and phone can drastically increase women's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives.", "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.", "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.", "Despite the burden of colorectal cancer and improved health care outcomes with early detection and treatment, screening rates among eligible adults are low. We previously developed through a series of studies an interactive electronic tool, Colorectal Web, to promote colorectal cancer screening.\n From May 2002 to December 2003, we conducted a randomized controlled trial of Colorectal Web compared to a standard Web site on colorectal cancer screening in urban, suburban, and rural communities in Michigan with high colorectal cancer burden. Study participants were age 50 years and older, with no previous colorectal cancer screening. Major outcome was screened for colorectal cancer by 24 weeks post-intervention.\n 174 eligible adults were randomized and participated. Immediately post-intervention, Colorectal Web participants were significantly more likely to have a preferred colorectal cancer screening method, but this difference did not persist at subsequent follow-up. Eighty-nine participants had been screened for colorectal cancer by 24 weeks post-intervention. The probability of being screened for the Colorectal Web intervention study arm compared to the control is OR=3.23 (2.73-3.50 95% Confidence Interval).\n Colorectal Web is more effective than a standard colorectal cancer Web site at prompting previously unscreened individuals to choose a preferred colorectal cancer screening test and to be screened for colorectal cancer.", "To assess whether providing women with additional information on the pros and cons of screening, compared with information currently offered by the NHS, affects their intention to attend for screening.\n Randomised controlled trial. Participants were randomly assigned to receive either the control, (based on an NHS Cervical Screening Programme leaflet currently used), or the intervention leaflet (containing additional information on risks and uncertainties).\n Three general practices in Birmingham.\n 300 women aged 20 to 64 attending the practices during a one month period.\n Intention to attend for screening. Main results: 283 women (94.3%) completed the study. Fewer women in the intervention (79%) than the control group (88%) expressed intention to have screening after reading the information leaflet (difference between groups 9.2%, 95% confidence intervals (CI) 3.2% to 21.7%). The crude odds ratio (OR) and 95% CI was 0.50 (0.26 to 0.97). After adjusting for other factors, the trend persisted (OR 0.60, 95% CI 0.28 to 1.29). Having a previous Pap smear was the only significant predictor of intention to have screening (adjusted OR 2.54, 95% CI 1.03 to 6.21). Subgroup analysis showed no intervention effect in intended uptake between women at higher and lower risk of cervical cancer (p=0.59).\n Providing women with evidence based information on the risks, uncertainties, and the benefits of screening, is likely to deter some, but not differentially those at higher risk.", "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.", "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.", "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).", "Screening mammography is recommended for early detection of breast cancer but screening rates remain suboptimal.\n A primary care portal for a large academic primary practice was developed for all preventive services. Another Web-based system (PRECARES [PREventive CAre REminder System]) was developed for appointment secretaries to manage proactive breast cancer screening. Female patients aged 40 to 75 years were randomly assigned to a control group (usual care) and an intervention group. For the intervention group, 2 monthly letters inviting patients to undergo mammography were sent starting 3 months before they were due for annual screening, followed by a telephone call to nonresponding patients. A subgroup of women employees was further randomized to receive a reminder by either US mail or e-mail.\n Of the total eligible population of 6665 women identified as having consented to participate in research, 3339 were randomly assigned to the control group and 3326 to the intervention group. The screening rate for annual mammography was 64.3% for the intervention group and 55.3% for the control group (P <.001). There were no significant differences between the 2 groups for any of the other adult preventive services. For the employee subgroup, the screening rate was 57.5% for the control group, 68.1% for the US mail group, and 72.2% for the e-mail group (intervention vs control, P <.001; e-mail vs US mail; P = .24).\n The breast cancer screening rate improved significantly with the practice redesign of having appointment secretaries proactively manage breast cancer screening needs.", "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.", "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.", "To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services.\n A randomised trial of two interventions alone and in combination.\n Physicians in 98 ambulatory care practices in the United States.\n The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets.\n The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute.\n Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing.\n Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.", "To explore women's reactions to 'informed choice' in mammographic screening.\n Telephone interviews with a convenience sample of 106 women aged 45-70 years recruited from general practices in Sydney.\n Many (42%) women preferred an active role in decision-making. Respondents had low scores for 'uncertainty' and 'factors contributing to uncertainty' in response to explicit questions about the decision to have mammographic screening. Yet respondents indicated significantly greater willingness to have a test when the benefit of a 'new' screening test for breast cancer was expressed as relative risk reduction (RRR) (88%) than either absolute risk reduction (ARR) (78%) (McNemar's test: chi(2)1=7.14, p=0.013) or all-cause mortality (53%) (McNemar's test: chi(2)1=35.1, p<0.01). Significantly more respondents considered information about ARR 'new' to them (65%) compared with RRR information (30%) (McNemar's test: chi(2)1=25.83, p<0.01).\n As mammographic screening exposes well women to potential harms for an overall population benefit, it is challenging to ensure 'informed choice'. Our results suggest women will likely appreciate individual consultations as the context in which to share complex information that women in our study agreed they need to know about mammographic screening. Our results also demonstrate that women's willingness as individuals to participate in mammographic screening is influenced by 'framing effect'. Hence, the quantitative content of decision aids to promote 'informed choice' must be comprehensive and balanced.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "Rates of colon cancer screening in the United States are low, in part because of poor communication between patients and providers about the availability of effective screening options.\n To test whether a decision aid consisting of an educational video, targeted brochure, and chart marker increased performance of colon cancer screening in primary care practices.\n Randomized, controlled trial.\n Three community primary care practices in central North Carolina.\n 1657 consecutive adult patients 50 to 75 years of age were contacted. Of these, 651 (39%) agreed to participate; 249 of the 651 participants (38%) were eligible. Eligible patients had no personal or family history of colon cancer and had not had fecal occult blood testing in the past year or flexible sigmoidoscopy, colonoscopy, or barium enema in the past 5 years.\n The 249 participants were randomly assigned to view an 11-minute video about colon cancer screening (intervention group) or a video about automobile safety (control group). After viewing the video, intervention group participants chose a color-coded educational brochure (based on stages of change) to indicate their degree of interest in screening. A chart marker of the same color was attached to their charts. Controls received a generic brochure on automobile safety, and no chart marker was attached.\n Frequency of screening test ordering as reported by participants and frequency of completion of screening tests as verified by chart review.\n Fecal occult blood testing or flexible sigmoidoscopy was ordered for 47.2% of intervention participants and 26.4% of controls (difference, 20.8 percentage points [95% CI, 8.6 to 32.9 percentage points]). Screening tests were completed by 36.8% of the intervention group and 22.6% of the control group (difference, 14.2 percentage points [CI, 3.0 to 25.4 percentage points]).\n A decision aid consisting of an educational video, brochure, and chart marker increased ordering and performance of colon cancer screening tests.", "To determine effective methods of promoting routine cancer screening, we randomly assigned 62 internal medicine residents to receive cancer screening reminders (computer-generated lists of overdue tests at patients' visits), audit with feedback (monthly seminars about screening, with feedback about their performance rates), or no intervention (controls). Half of the residents in each group also were randomized to receive patient education (patients received literature and notices of overdue tests). We reviewed a sample of each physician's medical records to assess performance of seven tests during 9-month periods before and after initiating the interventions. Cancer screening reminders increased performance of six of seven tests; audit with feedback, four of seven tests; and patient education, one of two targeted breast cancer screening tests. The results indicate that the cancer screening reminders strategy was the most effective in promoting the performance of routine cancer screening tests.", "To assess the comparative efficacy, by randomised controlled trial, of three interventions designed to encourage \"at risk\" women to have a Pap smear: an educational pamphlet; letters inviting attendance at a women's health clinic; and letters from physicians.\n Subjects at risk for cervical cancer who had not been adequately screened were identified by a random community survey and randomly allocated to one of the intervention groups or a control group. Six months after intervention implementation, a follow up survey assessed subsequent screening attendance. Self report was validated by comparison with a national screening data base.\n A significantly greater proportion of women (36.9%) within the group receiving a physician letter reported screening at follow up than in any other group (P = 0.012). The variables most strongly predicting screening attendance were: age, perceived frequency of screening required, use of oral contraceptives, and allocation to receive the physician letter intervention.\n The relative efficacy of the GP letter in prompting screening attendance shows that this strategy is worthy of further investigation. There remains a need to examine the barriers to screening for older women, and to develop tailored strategies for this population.", "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.", "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.", "This study was conducted to evaluate the feasibility of using a computer intervention to enhance communication between healthcare professionals and women with breast cancer. Additional aims were to measure the extent to which women achieved their preferred decisional roles and satisfaction with the clinical medical appointment. This two-arm randomized clinical trial design included a convenience sample of 749 women with breast cancer attending 3 urban Canadian outpatient oncology clinics. Most women were older than 50 years and had a high school diploma or greater (57%). Women in the control group completed measures of decision preference before their clinic appointments. Women in the intervention group were encouraged to use the information and decision preference profiles generated by the computer program at their clinic appointments. Levels of involvement in decision making and satisfaction were measured after the clinic appointments. Results showed that although the majority of women in both groups did assume their preferred roles in decision making, a significantly higher proportion of women in the intervention group reported playing a more passive role than originally planned. Both groups reported high satisfaction levels. Future research is required to study how this computer intervention could be used by clinicians to provide information and decision support to these women.", "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.", "Despite increased interest among the public in breast cancer genetic risk and genetic testing, there are limited services to help women make informed decisions about genetic testing. This study, conducted with female callers (N = 279) to the National Cancer Institute's (NCI's) Atlantic Region Cancer Information Service (CIS), developed and evaluated a theory-based, educational intervention designed to increase callers' understanding of the following: (a) the kinds of information required to determine inherited risk; (b) their own personal family history of cancer; and (c) the benefits and limitations of genetic testing. Callers requesting information about breast/ovarian cancer risk, risk assessment services, and genetic testing were randomized to either: (1) standard care or (2) an educational intervention. Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months. In addition, high monitors, who typically attend to and seek information, demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors, who typically are distracted from information. These findings suggest that theoretically designed interventions can be effective in helping women understand their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS.", "Although colorectal cancer screening by using a fecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy, or barium enema x-ray reduces the incidence of and death from colorectal cancer, the rate of colorectal cancer screening in the general population is low. We conducted a randomized trial consisting of direct mailing of FOBT kits to increase colorectal cancer screening among residents of Wright County, Minnesota, a community in which colorectal cancer screening was promoted.\n At baseline, we mailed a questionnaire about colorectal cancer screening to a random sample of Wright County residents aged 50 years or older who were randomly selected from the Minnesota State Driver's License and Identification Card database (estimated N = 1451). The sample was randomly allocated into three equal subgroups: one group (control) received only the questionnaire, one group received FOBT kits by direct mail with reminders, and one group received FOBT kits by direct mail without reminders. Study participants were sent a follow-up questionnaire 1 year after baseline. We used the responses to the questionnaires to estimate the 1-year change in self-reported screening rates in each group and the differences in the changes among the groups, along with the associated bootstrap 95% confidence intervals (CIs).\n At baseline, the estimated response rate was 86.5%, self-reported adherence to FOBT guidelines was 21.5%, and overall adherence to any colorectal cancer screening test guidelines was 55.8%. The 1-year rate changes in absolute percentage for self-reported adherence to FOBT use were 1.5% (95% CI = -2.9% to 5.9%) for the control group, 16.9% (95% CI = 11.5% to 22.3%) for the direct-mail-FOBT-with-no-reminders group, and 23.2% (95% CI = 17.2% to 29.3%) for the direct-mail-FOBT-with-reminders group. The 1-year rate changes for self-reported adherence to any colorectal cancer screening test were 7.8% (95% CI = 3.2% to 12.0%) for the control group, 13.2% (95% CI = 8.4% to 18.2%) for the direct-mail-FOBT-with-no-reminders group, and 14.1% (95% CI = 9.1% to 19.1%) for the direct-mail-FOBT-with-reminders group.\n Direct mailing of FOBT kits combined with follow-up reminders promotes more rapid increases in the use of FOBT and nearly doubles the increase in overall rate of adherence to colorectal cancer screening guidelines in a general population compared with a community-wide screening promotion and awareness campaign.", "This study was aimed at evaluating the effects of an education program for general practitioners on their prescribing behaviour for cervical and breast cancer screening tests, and assessing the feasibility of general practitioners participation in screening programs. All three cytology laboratories and 19 of the 20 radiologists in one administrative region (\"Haute-Savoie\") in France agreed to participate. The 278 general practices in this region were randomly assigned to either the intervention group (a one-day seminar on screening for breast cancer and cervical cancer) or the control group (n for both = 139). The prescriptions of tests for the following year were noted from the laboratories' and radiologists' records. No significant differences were observed between the intervention group and the control group for the number of mammographies prescribed with a mean of 19.3 and 15.2 per practice, respectively. However, significantly more mammographies were prescribed in women aged over 50 by the intervention group (p = 0.038). Inversely, fewer smear tests were prescribed in the intervention group (mean per practice: 40.5 and 46.1, respectively). A significantly higher number of practices in the intervention group did not prescribe any smear tests (p = 0.007). This study suggests that it is possible to influence general practitioners' participation in screening programs, but that the messages should be carefully presented, since negative effects are possible." ]

[ "15998750", "16770975", "1477566", "18758677", "11246937", "8912507", "19501658" ]

[ "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.", "Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial.", "A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia.", "Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs)." ]

[ "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.", "To test effectiveness of static magnetic fields of two different configurations, produced by magnetic sleep pads, as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia.\n Randomized, placebo-controlled, 6-month trial conducted from November 1997 through December 1998.\n Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic.\n Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low, uniform static magnetic field of negative polarity. Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity. Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets; these groups were combined for analysis. Subjects in the Usual Care group continued with their established treatment regimens.\n Primary outcomes were the change scores at 6 months in the following measures: functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings, tender point count, and a tender point pain intensity score.\n There was a significant difference among groups in pain intensity ratings (p = 0.03), with Functional Pad A group showing the greatest reduction from baseline at 6 months. All four groups showed a decline in number of tender points, but differences among the groups were not significant (p = 0.72). The functional pad groups showed the largest decline in total tender point pain intensity, but overall differences were not significant (p = 0.25). Improvement in functional status was greatest in the functional pad groups, but differences among groups were not significant (p = 0.23).\n Although the functional pad groups showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months of treatment, with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group.", "To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).\n Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.\n Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.\n Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.", "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." ]

[ "7498892", "8353699", "7953031", "475542", "9545998" ]

[ "Toward managed care for persons with severe mental illness: implications from a cost-effectiveness study.", "A controlled trial of home-based acute psychiatric services. I: Clinical and social outcome.", "Home-based versus hospital-based care for people with serious mental illness.", "A comparative trial of home and hospital psychiatric care. One-year follow-up.", "Randomized trial of general hospital and residential alternative care for patients with severe and persistent mental illness." ]

[ "Over the past two decades various models of community-based care for persons with severe mental illness have been developed. This study, which represents the first comparison of the most successful care approach (Program of Assertive Community Treatment or PACT adaptation model) with other, less intensive approaches (clinical team and intensive broker models) in a community service system, indicates that client outcomes were more positive in the PACT adaptation model in terms of enhanced psychosocial functioning and reduced acute and subacute care costs. The PACT model was not significantly more expensive in terms of the costs of providing supportive services compared with the clinical team approach and the intensive broker model of care.", "While research has shown community-based psychiatric care to be as good as, or better than, hospital-based care, generalisation to clinical practice has been difficult. This prospective, randomised controlled study examined a community-based approach feasible within NHS conditions. Ninety-four patients were randomly allocated to experimental and 78 to control treatments and followed for one year. The groups were well matched apart from an excess of psychotic control patients. No differences in clinical or social functioning outcome were found. Both groups improved substantially on clinical measures in the first six weeks, with some slow consolidation thereafter. There were three suicides in the control group and one in the experimental group. Access to care was better in the experimental group (93% attended assessment) than in the control group (75% attended assessment).", "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.", "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.", "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." ]

[ "8688397", "9492730", "8623871", "2030849", "9740522", "11423890", "1988896", "15515998", "15983684" ]

[ "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 or nonclosure of the visceral peritoneum at cesarean delivery.", "A randomized study of closure of the peritoneum at cesarean delivery.", "Closure versus non-closure of peritoneum at cesarean section--evaluation of pain. A randomized study.", "A randomized controlled study of peritoneal closure at cesarean section.", "Peritoneal closure or non-closure at cesarean.", "Closure vs non-closure of the visceral and parietal peritoneum at cesarean delivery: 16 year study.", "Closure or nonclosure of the peritoneum at gynecological operations. Effect on postoperative pain." ]

[ "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.", "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.", "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 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.", "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.", "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.", "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 compare the analgesic requirement and pain scores in the postoperative period between closure and nonclosure of the peritoneum in women undergoing gynecological abdominal surgery.\n We conducted this study as a 2 parallel grouped, double blind, randomized, controlled trial between February 2002 and March 2003. The current study consists of 79 eligible women who were enrolled and completed baseline assessments. We carried out this study at the Cumhuriyet University Hospital, Sivas, Turkey.\n When the age, gravidity, parity, body mass index, type of surgery, operative time and length of hospital stay were compared, between the 2 groups, no statistically significant difference was found (p>0.05). The postoperative pain was found higher in the closure group than the nonclosure group (p<0.05) when the pain with visual analogue scale (VAS) scores compared.\n There was no significant difference in analgesic requirements between the 2 groups in the postoperative period. However, less pain and low VAS scores were evident especially after postoperative 2nd and 48th hours in the nonclosure group. We recommend non-closure of peritoneum at abdominal gynecologic procedure as the method of choice." ]

[ "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." ]

[ "7413719", "1839644", "8964276" ]

[ "Chronic administration of cannabidiol to healthy volunteers and epileptic patients.", "Controlled clinical trial of cannabidiol in Huntington's disease.", "A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy." ]

[ "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.", "Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.", "The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated, newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures, were compared in a randomised, open, multicentre study. Patients received 24 weeks' treatment with oral lamotrigine 100 mg (LTG 100, n = 115) or 200 mg (LTG 200, n = 111) or carbamazepine 600 mg (CBZ 600, n = 117). Efficacy measurements were comparable between the three treatment groups, although the higher lamotrigine dose was possibly most effective, with 60.4% completing seizure free compared with 51.3% (LTG 100) and 54.7% (CBZ 600). Both dosage regimens of lamotrigine were well tolerated. More patients on CBZ 600 reported adverse experiences, 66% versus 53% (LTG 100) and 58% (LTG 200), and of these a greater proportion were attributed to CBZ 600 treatment, 53% versus 23% (LTG 100) and 28% (LTG 200). Similarly, a greater proportion of the CBZ 600 group required a change in dose, 47% versus 20% (LTG 100) and 17% (LTG 200) or withdrew completely due to adverse experiences, 10.3% versus 4.3% (LTG 100) and 4.5% (LTG 200). The most common adverse experience leading to withdrawal was rash, with approximately double the proportion of reports occurring in patients on CBZ 600 (5.1%) compared with lamotrigine (1.7% on LTG 100 and 2.7% on LTG 200). Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine." ]

[ "6853785" ]

[ "Once-daily treatment of psoriasis with topical glucocorticosteroid ointments." ]

[ "A double-blind, vehicle-controlled comparison of two glucocorticosteroid ointments demonstrated that once-daily therapy for psoriasis was effective. After 3 weeks of once-daily therapy, psoriasis subjects treated with betamethasone dipropionate (BD) ointment or diflorasone diacetate (DD) ointment showed statistically significant (p less than 0.01) improvement compared to subjects using vehicle alone." ]

[ "15585539", "15377573", "18417560", "15089956", "17055767", "7041850", "1532760", "17678655", "9549021", "18295614", "12455427", "1559090", "18637956", "20531162", "19940729", "11837056", "19261602", "15911154", "11391327", "11944742", "15774435" ]

[ "Randomised trial of a brief physiotherapy intervention compared with usual physiotherapy for neck pain patients: outcomes and patients' preference.", "Randomised controlled trial of physiotherapy compared with advice for low back pain.", "A randomised controlled trial on whether a participatory ergonomics intervention could prevent musculoskeletal disorders.", "Evidence-based postoperative pain management in nursing: is a randomized-controlled trial the most appropriate design?", "Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial.", "Electromyographic feedback in the remobilization of stroke patients: a controlled trial.", "Randomised clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up.", "Circuit class therapy versus individual physiotherapy sessions during inpatient stroke rehabilitation: a controlled trial.", "Electromyographic biofeedback for gait training after stroke.", "Whole body vibration versus conventional physiotherapy to improve balance and gait in Parkinson's disease.", "A randomized clinical trial of a tailored comprehensive care treatment program for temporomandibular disorders.", "Physiotherapy intervention late after stroke and mobility.", "TENS and optokinetic stimulation in neglect therapy after cerebrovascular accident: a randomized controlled study.", "Therapeutic exercise during outpatient radiation therapy for advanced cancer: Feasibility and impact on physical well-being.", "Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: a randomized clinical trial.", "Randomized controlled trial of back school with and without peer support.", "Prophylactic cavotricuspid isthmus block during atrial fibrillation ablation in patients without atrial flutter: a randomised controlled trial.", "A 3-year follow-up of a multidisciplinary rehabilitation programme for back and neck pain.", "Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis.", "Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.", "Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial." ]

[ "Firstly, to compare the effectiveness of a brief physiotherapy intervention with \"usual\" physiotherapy for patients with neck pain. Secondly, to evaluate the effect of patients' preferences on outcome.\n Non-inferiority randomised controlled trial eliciting preferences independently of randomisation.\n Physiotherapy departments in a community setting in Yorkshire and north Lincolnshire.\n 268 patients (mean age 48 years) with subacute and chronic neck pain, who were referred by their general practitioner and randomly assigned to a brief physiotherapy intervention (one to three sessions) using cognitive behaviour principles to encourage self management and return to normal function or usual physiotherapy, at the discretion of the physiotherapist concerned.\n The Northwick Park neck pain questionnaire (NPQ), a specific measure of functional disability resulting from neck pain. Also, the short form 36 (SF-36) questionnaire, a generic, health related, quality of life measure; and the Tampa scale for kinesophobia, a measure of fear and avoidance of movement.\n At 12 months, patients allocated to usual physiotherapy had a small but significant improvement in NPQ scores compared with patients in the brief intervention group (mean difference 1.99, 95% confidence interval 0.45 to 3.52; P = 0.01). Although the result shows a significant inferiority of the intervention, the confidence interval shows that the effect could be in the non-inferiority range for the brief intervention (below 1.2 points of NPQ score). Patients who preferred the brief intervention and received this treatment had similar outcomes to patients receiving usual physiotherapy.\n Usual physiotherapy may be only marginally better than a brief physiotherapy intervention for neck pain. Patients with a preference for the brief intervention may do at least as well with this approach. Additional training for the physiotherapists in cognitive behaviour techniques might improve this approach further.", "To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain.\n Pragmatic, multicentre, randomised controlled trial.\n Seven British NHS physiotherapy departments.\n 286 patients with low back pain of more than six weeks' duration.\n Routine physiotherapy or advice on remaining active from a physiotherapist. Both groups received an advice book.\n Primary outcome was scores on the Oswestry disability index at 12 months. Secondary outcomes were scores on the Oswestry disability index (two and six months), scores on the Roland and Morris disability questionnaire and SF-36 (2, 6 and 12 months), and patient perceived benefit from treatment (2, 6, and 12 months).\n 200 of 286 patients (70%) provided follow up information at 12 months. Patients in the therapy group reported enhanced perceptions of benefit, but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures (mean difference in change in Oswestry disability index scores at 12 months -1.0%, 95% confidence interval -3.7% to 1.6%). The most common treatments were low velocity spinal joint mobilisation techniques (72%, 104 of 144 patients) and lumbar spine mobility and abdominal strengthening exercises (94%, 136 patients).\n Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist.", "To examine the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders among kitchen workers. Participatory ergonomics is commonly recommended to reduce musculoskeletal disorders, but evidence for its effectiveness is sparse.\n A cluster randomised controlled trial among the 504 workers of 119 kitchens in Finland was conducted during 2002-2005. Kitchens were randomised to an intervention (n = 59) and control (n = 60) group. The duration of the intervention that guided the workers to identify strenuous work tasks and to seek solutions for decreasing physical and mental workload, was 11 to 14 months. In total, 402 ergonomic changes were implemented. The main outcome measures were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local fatigue after work, and sick leave due to musculoskeletal disorders. Individual level data were collected by a questionnaire at baseline and every 3 months during the intervention and 1-year follow-up period. All response rates exceeded 92%.\n No systematic differences in any outcome variable were found between the intervention and control groups during the intervention or during the 1-year follow-up.\n The intervention did not reduce perceived physical work load and no evidence was found for the efficacy of the intervention in preventing musculoskeletal disorders among kitchen workers. It may be that a more comprehensive redesign of work organisation and processes is needed, taking more account of workers' physical and mental resources.", "There is an increasing drive to make nursing care evidence-based. High quality evidence from systematic reviews relevant to postoperative pain relief exists, yet pain after surgery remains poorly controlled for many patients. This study aimed to assess whether implementing evidence-based pain management improved postoperative pain outcomes. Pain on a 0-10 scale was the primary outcome and analgesic consumption a secondary outcome. A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study. A randomized-controlled trial was then designed to assess the effects of implementing an evidence-based approach to postoperative pain management. The four wards were randomized to receive the intervention or act as a control. Outcomes were assessed 3 months after the intervention on both intervention and control wards. The intervention (implementation of an oral analgesic algorithm derived from systematic reviews) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards. The intervention was designed using an evidence-based approach to effective implementation. Four interactive sessions covered: (1) detailed feedback of baseline data and discussion (utilizing audit and feedback), (2) why systematic reviews, analgesic league tables and choice of drugs to develop an analgesic algorithm (see Figure 1), (3) principles of evidence based health care (EBHC), including critical appraisal and (4) facilitation and change workshop. The findings revealed no significant differences in pain level or drug use between the intervention and control wards. However, the control wards also changed during the control period. Possible explanations for this are discussed. When looking at changes compared with baseline, both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study. No effects were found on pain in the intervention wards. Pain ratings at rest since surgery, on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards. Although there are many pressures to utilize a randomized-controlled trial study design in the culture of evidence-based health care, there will be times, especially when implementing complex changes in practice that other types of design should be considered.", "To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome measures were the Parkinson's disease questionnaire-39, the Parkinson activity scale, and a patient preference outcome scale (PPOS). Only 14% of the patients could be included in the study. The PPOS showed the largest effect size (0.74) with a significant group effect (p<0.05). Specific alterations to the study design to ensure successful RCTs in this field are recommended.", "Electromyographic biofeedback was compared with simple exercise therapy as to its effectiveness in improving foot-drop in 22 stroke patients. The study was designed to be a rigorous trial of biofeedback and the patients tested were aged and had stroke of long duration. One group of 11 patients underwent 6 weeks of exercise therapy 2 sessions per week for 15 minutes per session; the 2nd group of 11 patients underwent similar therapy with EMG feedback. All therapy was conducted by a research assistant who was not a trained therapist. The groups were assessed blind before treatment, after treatment and a 6-week follow-up. The significantly greater improvements in the biofeedback group in terms of muscle strength at the end of treatment were maintained at follow-up. On the range of movement and gait analysis measures, both groups showed some improvement after treatment. However, at follow-up this improvement had relapsed for the exercise group while for the biofeedback group it had been maintained. It is argued that controlled trials are possible in biofeedback and that using patients as their own controls is not justified in view of the present findings and the previously reported literature.", "To compare the effectiveness of manipulative therapy, physiotherapy, treatment by the general practitioner, and placebo therapy in patients with persistent non-specific back and neck complaints.\n Randomised clinical trial.\n Primary health care in the Netherlands.\n 256 patients with non-specific back and neck complaints of at least six weeks' duration who had not received physiotherapy or manipulative therapy in the past two years.\n At the discretion of the manipulative therapists, physiotherapists, and general practitioners. Physiotherapy consisted of exercises, massage, and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manipulative therapy consisted of manipulation and mobilisation of the spine. Treatment by general practitioners consisted of drugs (for example, analgesics), advice about posture, home exercises, and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 minutes) and detuned ultrasound (10 minutes).\n Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients.\n Many patients in the general practitioner and placebo groups received other treatment during follow up. Improvement in the main complaint was larger with manipulative therapy (4.5) than with physiotherapy (3.8) after 12 months' follow up (difference 0.9; 95% confidence interval 0.1 to 1.7). Manipulative therapy also gave larger improvements in physical functioning (difference 0.6; -0.1 to 1.3). The global perceived effect after six and 12 months' follow up was similar for both treatments.\n Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment. Furthermore, manipulative therapy is slightly better than physiotherapy after 12 months.", "To compare the effectiveness of circuit class therapy and individual physiotherapy (PT) sessions in improving walking ability and functional balance for people recovering from stroke.\n Nonrandomized, single-blind controlled trial.\n Medical rehabilitation ward of a rehabilitation hospital.\n Sixty-eight persons receiving inpatient rehabilitation after a stroke.\n Subjects received group circuit class therapy or individual treatment sessions as the sole method of PT service delivery for the duration of their inpatient stay.\n Five-meter walk test (5MWT), two-minute walk test (2MWT), and the Berg Balance Scale (BBS) measured 4 weeks after admission. Secondary outcome measures included the Iowa Level of Assistance Scale, Motor Assessment Scale upper-limb items, and patient satisfaction. Measures were taken on admission and 4 weeks later.\n Subjects in both groups showed significant improvements between admission and week 4 in all primary outcome measures. There were no significant between group differences in the primary outcome measures at week 4 (5MWT mean difference, .07m/s; 2MWT mean difference, 1.8m; BBS mean difference, 3.9 points). A significantly higher proportion of subjects in the circuit class therapy group were able to walk independently at discharge (P=.01) and were satisfied with the amount of therapy received (P=.007).\n Circuit class therapy appeared as effective as individual PT sessions for this sample of subjects receiving inpatient rehabilitation poststroke. Favorable results for circuit classes in terms of increased walking independence and patient satisfaction suggest this model of service delivery warrants further investigation.", "To examine the effects of electromyographic (EMG) biofeedback training on the recovery of gait in the acute phase post stroke.\n Patients were randomly assigned to EMG biofeedback or control groups. They received treatment three times a week for six weeks. All patients were assessed prior to treatment, after 18 treatment sessions, and at three months follow-up.\n The study was carried out at Scunthorpe General Hospital in North Lincolnshire. The subjects were acute stroke patients who had been admitted on to the medical and elderly wards.\n The EMG biofeedback group were treated using EMG as an adjunct to physiotherapy. The patients were encouraged to facilitate or inhibit abnormal muscle tone via auditory or visual signals transmitted from electrodes placed over the appropriate muscles. The control group were treated using the same techniques, electrodes were used with this group of patients, but the EMG machine was turned off and faced away from the patient and the therapist to control the placebo effect.\n A large battery of outcome measures was used for physical and psychological assessment. The physical measures consisted of active movement, muscle tone, sensation, proprioception, mobility and activities of daily living (ADL). The psychological measures included orientation, memory, spatial performance, language and IQ.\n Twenty-one patients were included in the study. Scores were combined into four groups: mild EMG, severe EMG, mild control and severe control. Results showed that there was an improvement in physical scores for active movement, mobility and ADL over time, but there was no significant difference between the EMG and control groups. Scores on the psychological tests were within normal limits, and there was no difference in performance between the EMG and control groups.\n This study showed no significant differences in the rate of improvement after stroke between the two groups. Although EMG biofeedback was used as an adjunct to physiotherapy and represented clinical practice, the results provide little evidence to support the clinical significance of using EMG biofeedback to improve gait in the acute phase after stroke.", "To compare the effects of whole body vibration (WBV) and conventional physiotherapy (PT) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson's disease (PD).\n Randomized controlled rater-blinded trial comparing 2 active interventions, final follow-up assessment 4 weeks after termination of active intervention.\n Specialized referral center, hospitalized care.\n Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication (N=27) were randomized (intent-to-treat population) to receive WBV (n=13) or conventional PT (controls, n=14). Twenty-one patients (per protocol population) completed follow-up (14 men, 7 women; mean age, 73.8 y; age range, 62-84 y; mean disease duration, 7.2 y; mean dopa-equivalent dose, 768 mg/d).\n Subjects were randomized to receive 30 sessions (two 15-min sessions a day, 5 days a week) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board. Twenty-one subjects (10 with WBV, 11 controls) were available for follow-up 4 weeks after treatment termination.\n The primary measure was Tinetti Balance Scale score. Secondary clinical ratings included stand-walk-sit test, walking velocity, Unified Parkinson's Disease Rating Scale (section III motor examination) score, performance in the pull test, and dynamic posturography.\n The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls. All secondary measures, except posturography, likewise improved at follow-up compared with baseline in both groups. Quantitative dynamic posturography only improved in patients with WBV (1937-1467 mm) whereas there was no significant change in controls (1832-2030 mm).\n Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program. There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training.", "To test the usefulness of tailoring cognitive-behavioral therapy (CBT) for patients with temporomandibular disorders (TMD) who demonstrated poor psychosocial adaptation to their TMD condition, independent of physical diagnosis.\n A randomized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists. For study inclusion, Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), Axis II criteria, were used to target patients with elevated levels of TMD pain-related interference with daily activities, independent of physical diagnosis (i.e., Axis I).\n At the post-treatment assessment, about 4 months after the baseline evaluations, the comprehensive care group, when compared to the usual treatment group, showed significantly lower levels of characteristic pain intensity, significantly higher self-reported ability to control their TMD pain, and a strong trend (P = .07) toward lower pain-related interference in daily activities. From post-intervention to 1-year follow-up, all subjects showed improvement. At the 1-year follow-up, the comprehensive care group, while not losing any of its early gains, was not significantly different from the usual care group with regard to reported levels of pain, ability to control pain, and levels of interference in activities. For many of these psychosocially disabled TMD patients, pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate randomized clinical trial on the basis of better psychosocial adaptation.\n The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment, but was too brief an intervention to result in further improvement after the sessions ended. Patient ratings of treatment satisfaction and helfulness were high for both groups, but they were significantly higher for the comprehensive care group.", "To determine whether the intervention of a physiotherapist improved mobility in patients seen more than one year after stroke.\n Randomised crossover trial comparing two groups offered intervention by a physiotherapist, one immediately after entry into the trial and the other after a delay of three months. The intervention consisted of identifying problems and offering advice and help to solve the problems.\n Patients' homes in Oxfordshire.\n Patients who had reduced mobility due to a stroke more than one year before entry; 60 were recruited from a community stroke register and 34 in other ways.\n Standard measures of mobility including gait speed, functional ambulation categories, the Nottingham extended activities of daily living index, and individual items from the Barthel activities of daily living index and the Frenchay activities index. Measures of manual dexterity, depression, and anxiety were used as controls.\n 94 patients entered the trial and 49 were randomised to immediate and 45 to delayed physiotherapy; 89 were compared at the crossover point. At randomisation the two groups were comparable. At three months the group given early therapy showed an improvement in gait speed whereas the untreated group had declined (differences of -3.9 v 6.4 s to walk 10 m; p less than 0.01); between three and six months the group given delayed therapy showed improvement and the previously treated group declined (differences of 6.5 v -3.9 s to walk 10 m; p less than 0.01). A 9% (95% confidence interval 0% to 18%) decrease in time taken to walk 10 m was associated with treatment and a 12% (2% to 19%) increase when patients were untreated. Other measures did not change significantly.\n Intervention of an experienced physiotherapist late after stroke specifically improves mobility, albeit by a small amount, but the effects do not seem to be maintained, perhaps because there is an underlying decline in mobility in these patients. Gait speed offers a simple and sensitive measure of outcome.", "In a randomized controlled type Ib study, the effectiveness of three different forms of therapy for the treatment of visual neglect was assessed by comparing therapy outcomes in three groups of patients after cerebrovascular accidents.\n A control group received only standard exploration training, whilst the second and third group received exploration training combined with either contralateral transcutaneous electrical nerve stimulation (TENS) or optokinetic stimulation (OKS) respectively.\n It was found that exploration training alone resulted in no improvement on both standard neglect tests (NTs) and everyday-relevant measures of reading and writing performance. In contrast, the groups receiving TENS or OKS showed significant improvements in both sets of measures with the difference that for the TENS group the improvement in NT scores at the end of therapy had disappeared 1-week later. However, both treatments resulted in significant improvements in reading and writing which were still present upon retesting 1-week after the end of therapy.\n Both methods can be recommended for neglect therapy and are superior to exploration therapy alone.", "To characterize the feasibility of delivering a structured physical therapy (PT) program as part of a multidisciplinary intervention to patients undergoing outpatient radiation therapy for advanced cancer.\n A single-blinded, randomized, controlled trial at a quaternary medical center outpatient clinic. One hundred three adults undergoing radiation therapy for advanced cancer with prognoses > or =6 mos and 5-yr survival estimates < or =50% were randomized to usual care or participation in eight 90-min, multidisciplinary interventional sessions with 30 mins of each session devoted to PT. PT consisted of truncal and limb isodynamic strengthening targeting major upper- and lower-limb muscle groups as well as education and provision with instructional materials. Physical well-being and fatigue were assessed with Linear Analog Scale of Assessment. The Profile of Mood States-Short form, including Fatigue-Inertia and Vigor-Activity subscales, was also administered.\n PT session attendance was 89.3%. Relative to baseline, mean physical well-being Linear Analog Self Assessment scores at week 4 improved in the intervention group, 0.4 (SD, 23.6), and declined significantly in the control group, -10.0 (SD, 21.5) (P = 0.02). Fatigue and vigor were not significantly different between the groups. All intergroup differences had resolved at 8 and 27 wks. Baseline characteristics were not associated with the magnitude or direction of change in outcomes related to physical functioning.\n Delivery of a standardized resistive exercise PT intervention is feasible during outpatient radiation therapy and is associated with preserved physical well-being. However, benefits were not sustained, and fatigue was not affected.", "Randomized clinical trial.\n The purpose of this randomized clinical trial was to examine the generalizability of 3 different manual therapy techniques in a patient population with low back pain that satisfy a clinical prediction rule (CPR).\n Recently a CPR that identifies patients with LBP who are likely to respond rapidly and dramatically to thrust manipulation has been developed and validated. The generalizability of the CPR requires further investigation.\n A total of 112 patients were enrolled in the trial and provided demographic information and completed a number of self-report questionnaires including the Oswestry Disability Questionnaire (ODQ) and the Numerical Pain Rating Scale (NPRS) at baseline, 1-week, 4-weeks, and 6-months. Patients were randomly assigned to receive 1 of the 3 manual therapy techniques for 2 consecutive treatment sessions followed by exercise regimen for an additional 3 sessions. We examined the primary aim using a linear mixed model for repeated measures, using the ODQ and NPRS as dependent variables. The hypothesis of interest was the group by time interaction, which was further explored with pair-wise comparisons of the estimated marginal means.\n There was a significant group x time interaction for the ODQ (P < 0.001) and NPRS scores (P = 0.001). Pair-wise comparisons revealed no differences between the supine thrust manipulation and side-lying thrust manipulation at any follow-up period. Significant differences in the ODQ and NPRS existed at each follow-up between the thrust manipulation and the nonthrust manipulation groups at 1-week and 4-weeks. There was also a significant difference in ODQ scores at 6-months in favor of the thrust groups.\n The results of the study support the generalizability of the CPR to another thrust manipulation technique, but not to the nonthrust manipulation technique that was used in this study. In general, our results also provided support that the CPR can be generalized to different settings from which it was derived and validated. However, additional research is needed to examine this issue.", "The aim of this trial was to determine whether social interaction between patients with long-lasting nonspecific back pain reduces subjective or objective disability. The participants were selected from persons visiting an occupational health care unit because of back pain. After a clinical examination in a university clinic, subjects without a specific diagnosis and having no disabilities preventing active rehabilitation were selected for study. The subjects (n = 108) were randomized into treatment (n = 54) and control groups (n = 54). Altogether 18 study groups, 9 treatment groups and 9 groups for controls, were formed. Before starting the back schools altogether 15 subjects dropped out. Both the treatment groups (n = 47) and the controls (n = 46) attended a back school consisting of 10 lessons and demonstrations supervised by a physiotherapist. The participants in treatment groups, but not the controls, had physical exercise and social intercourse with other members within the group. The clinical examination was repeated after 6 and 12 months. Both the treatment groups and the controls showed improvement in perceived functional capacity (assessed with Oswestry disability questionnaire) and in perceived life quality (assessed with 15D score). At the 6-month follow-up life quality had improved statistically significantly more among the participants in treatment groups than among the controls, and at the 12-month follow-up the Oswestry index showed corresponding improvement. Among subjects suffering from nonspecific back pain, social support improves the results of active rehabilitation.", "This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA).\n 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n = 73) or CPVA alone (group CTIB-, n = 76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months.\n Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups (CTIB+: 88% vs CTIB-: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p = 0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB-: 32%, HR 0.93, 95% CI (0.63 to 1.38), p = 0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic.\n It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.", "The aim of the present study was to evaluate the long-term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components, compared to a 'treatment-as-usual' control group. The study employed a 4 x 5 repeated-measures design with four groups and five assessment periods during a 3-year follow-up. The group studied consisted of blue-collar and service/care workers on sick leave, identified in a nationwide health insurance scheme in Sweden. After inclusion, the subjects were randomised to one of the four conditions: behaviour-oriented physiotherapy (PT), cognitive behavioural therapy (CBT), behavioural medicine rehabilitation consisting of PT+CBT (BM) and a 'treatment-as-usual' control group (CG). Outcome variables were sick leave, early retirement and health-related quality of life. A cost-effectiveness analysis, comparing the programmes, was made. The results showed, consistently, the full-time behavioural medicine programme being superior to the three other conditions. The strongest effect was found on females. Regarding sick leave, the mean difference in the per-protocol analysis between the BM programme and the control group was 201 days, thus reducing sick leave by about two-thirds of a working year. Rehabilitating women has a substantial impact on costs for production losses, whereas rehabilitating men seem to be effortless with no significant effect on either health or costs. In conclusion, a full-time behavioural medicine programme is a cost-effective method for improving health and increasing return to work in women working in blue-collar or service/care occupations and suffering from back/neck pain.", "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.", "This study was planned to investigate the efficacy of neuromuscular rehabilitation and Johnstone Pressure Splints in the patients who had ataxic multiple sclerosis.\n Twenty-six outpatients with multiple sclerosis were the subjects of the study. The control group (n = 13) was given neuromuscular rehabilitation, whereas the study group (n = 13) was treated with Johnstone Pressure Splints in addition.\n In pre- and posttreatment data, significant differences were found in sensation, anterior balance, gait parameters, and Expanded Disability Status Scale (p < 0.05). An important difference was observed in walking-on-two-lines data within the groups (p < 0.05). There also was a statistically significant difference in pendular movements and dysdiadakokinesia (p < 0.05). When the posttreatment values were compared, there was no significant difference between sensation, anterior balance, gait parameters, equilibrium and nonequilibrium coordination tests, Expanded Disability Status Scale, cortical onset latency, and central conduction time of somatosensory evoked potentials and motor evoked potentials (p > 0.05). Comparison of values revealed an important difference in cortical onset-P37 peak amplitude of somatosensory evoked potentials (right limbs) in favor of the study group (p < 0.05).\n According to our study, it was determined that physiotherapy approaches were effective to decrease the ataxia. We conclude that the combination of suitable physiotherapy techniques is effective multiple sclerosis rehabilitation.", "Bobath based (BB) and movement science based (MSB) physiotherapy interventions are widely used for patients after stroke. There is little evidence to suggest which is most effective. This single-blind randomised controlled trial evaluated the effect of these treatments on movement abilities and functional independence.\n A total of 120 patients admitted to a stroke rehabilitation ward were randomised into two treatment groups to receive either BB or MSB treatment. Primary outcome measures were the Rivermead Motor Assessment and the Motor Assessment Scale. Secondary measures assessed functional independence, walking speed, arm function, muscle tone, and sensation. Measures were performed by a blinded assessor at baseline, and then at 1, 3, and 6 months after baseline. Analysis of serial measurements was performed to compare outcomes between the groups by calculating the area under the curve (AUC) and inserting AUC values into Mann-Whitney U tests.\n Comparison between groups showed no significant difference for any outcome measures. Significance values for the Rivermead Motor Assessment ranged from p = 0.23 to p = 0.97 and for the Motor Assessment Scale from p = 0.29 to p = 0.87.\n There were no significant differences in movement abilities or functional independence between patients receiving a BB or an MSB intervention. Therefore the study did not show that one approach was more effective than the other in the treatment of stroke patients." ]

[ "11273219", "12181464" ]

[ "Vaginal lavage with chlorhexidine during labour to reduce mother-to-child HIV transmission: clinical trial in Mombasa, Kenya.", "15 Month follow up of African children following vaginal cleansing with benzalkonium chloride of their HIV infected mothers during late pregnancy and delivery." ]

[ "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.", "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." ]

[ "12889565", "16009687", "15566514", "8665186" ]

[ "Comparison of percutaneous acetic acid injection and percutaneous ethanol injection for hepatocellular carcinoma in cirrhotic patients: 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.", "Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial.", "Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma." ]

[ "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.", "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.", "Transcatheter arterial embolization (TAE) may reduce the risk of hepatocellular carcinoma (HCC) recurrence when performed before percutaneous tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or radiofrequency ablation (RFA). We conducted a randomized, controlled trial comparing the use of TAE combined with percutaneous ethanol injection therapy (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and survival. We continued the study after the introduction of RFA and compared TAE combined with RFA (TAE/RFA) with RFA only.\n Between March 1997 and April 2001, 42 HCC patients were enrolled who satisfied the following inclusion criteria: (1) uninodular HCC as determined by angiography under computed tomography, (2) arterial hypervascularity, and (3) no prior history of HCC treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and 20 patients with PTA only (PEIT, 14; RFA, 6).\n There were four cases of local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043). The four patients with local recurrence were treated with PEIT. None of the patients treated with RFA showed local recurrence. The effect of TAE on overall recurrence was not significant (P=0.4179). In the multivariate analysis, prior TAE was not significant for survival (P=0.514).\n TAE has a limited use in suppressing local recurrence when performed before PEIT but not before RFA.", "Adjuvant oral chemotherapy was studied in 67 patients with stage II hepatocellular carcinoma who underwent curative resection between May 1988 and December 1990. Patients were stratified into two groups according to preoperative liver dysfunction: 55 had stage I disease (mild dysfunction) and 12 had stage II (moderate dysfunction). A randomized controlled study of postoperative oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) was conducted in each group. From October 1994 HCFU administration was suspended because of side-effects in nine patients with stage I liver dysfunction and in three with stage II dysfunction who had received the drug for more than 4 weeks. Cumulative survival and recurrence-free survival rates of patients with stage I disease in the treatment group were higher (P = 0.08 and P = 0.04 respectively) than those in the control group. However, in patients with stage II disease no significant difference was observed (P = 0.77 and P = 1.0 respectively). This study suggests that the potential benefits of HCFU on tumour recurrence should be weighed against the risk of adverse reactions in patients with mild liver dysfunction." ]

[ "16682258", "8147352", "2007362", "7797827", "8314510" ]

[ "Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial.", "Antimycobacterial therapy in Crohn's disease: results of a controlled, double-blind trial with a multiple antibiotic regimen.", "Controlled trial of antimycobacterial therapy in Crohn's disease. Clofazimine versus placebo.", "A controlled double blind multicenter study of the effectiveness of 5-aminosalicylic acid in patients with Crohn's disease in remission.", "Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial." ]

[ "Nutritional therapy has been reported to have an almost equivalent efficacy of corticosteroids in achieving clinical remission in active Crohn's disease (CD). However, the effects of both treatments on intestinal mucosal inflammation rarely are reported. In a randomized controlled trial in children with active CD we compared the efficacy of nutritional therapy alone or corticosteroids on clinical variables and intestinal mucosal healing.\n In a prospective, 10-week open-label trial, children with active, naive CD were randomized to orally polymeric formula alone or oral corticosteroids. The clinical activity index and nutritional and activity serum variables were evaluated at week 0 and then every 2 weeks; intestinal mucosal inflammation was assessed through endoscopy and histology at weeks 0 and 10. Primary efficacy outcomes were clinical remission and mucosal healing.\n Of the 37 children randomized, 19 received polymeric formula and 18 received corticosteroids. At week 10, on an intention-to-treat basis, the proportion of patients achieving clinical remission was comparable between the 2 groups (polymeric formula: 15/19 [79%; 95% confidence interval (CI), 56%-92%]; corticosteroid group: 12/18 [67%; 95% CI, 44%-84%]; P = .4; not significant). On the contrary, the proportion of children showing mucosa healing was significantly higher in the polymeric (14/19; 74%; 95% CI, 51%-89%) than the corticosteroid group (6/18 [33%; 95% CI, 16%-57%]; P < .05). At week 10 both endoscopic and histologic scores significantly decreased only in the polymeric group (P < .001).\n In children with active and recently diagnosed CD, a short course of polymeric diet is more effective than corticosteroids in inducing healing of gut inflammatory lesions.", "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.", "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.", "We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohn's disease. Included were 59 patients who had proven Crohn's disease of at least 1 year's duration, and who had been in continuous remission for at least 6 months, while taking only 5-aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohn's disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohn's disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years.", "Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease." ]

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[ "Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans.", "Cyclosporine-induced hypertension and decline in renal function in healthy volunteers.", "Sequential effects of cyclosporine therapy on blood pressure, renal function and neurohormones.", "The impact of lactotripeptides on blood pressure response in stage 1 and stage 2 hypertensives.", "Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.", "Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males.", "Blood pressure response to oral calcium in persons with mild to moderate hypertension. A randomized, double-blind, placebo-controlled, crossover trial.", "Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study.", "Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period.", "Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial.", "A controlled, double-blind, randomized trial of verapamil and cyclosporine in cadaver renal transplant patients.", "Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.", "Double-blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension.", "A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.", "Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial.", "Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial." ]

[ "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.", "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.", "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.", "Nearly 70 million Americans have hypertension, and approximately an equal number have prehypertension. The prevalence of both disorders increases with advancing age and obesity. Many at-risk individuals do not have controlled blood pressure (BP). Lifestyle modification for most persons is the first step in a plan to control these conditions. Non-drug treatments offer an appeal to many patients with modest BP elevation. The authors recently evaluated BP response using 24-hour ambulatory BP monitoring and office BP monitoring of lactotripeptides dosed twice daily in 91 previously treated and treatment-naive patients with stage 1 and stage 2 hypertension. In this population, daytime systolic BP, the primary efficacy end point, significantly decreased (-3.6 mm Hg; P=.013), while placebo did not affect systolic BP (0 mm Hg; P=not significant). Treatment-naive patients exhibited a more robust drop in their daytime systolic BP (-7.6 mm Hg; P=.005) compared with placebo (-3.6 mm Hg; P=not significant). Lactotripeptides may be an effective agent in the management of low-risk and low-grade hypertension and prehypertension.", "Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension.\n Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure.\n Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated.\n Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.", "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 blood pressure response of 48 hypertensive persons and 32 normotensive persons to elemental calcium (as the carbonate or citrate salt), 1000 mg/d for 8 weeks, was assessed in a randomized, double-blind, placebo-controlled, crossover trial. Compared with placebo, Ca2+ significantly lowered supine systolic blood pressure by 3.8 mm Hg, standing systolic blood pressure by 5.6 mm Hg (p less than 0.02), and supine diastolic blood pressure by 2.3 mm Hg (p less than 0.05) in hypertensive persons. The response in normotensive persons differed significantly from that in hypertensives (p less than 0.03) as their blood pressure was unchanged. Twenty-one (44%) hypertensive and 6 (19%) normotensive persons achieved a reduction in standing systolic arterial pressure of 10 mm Hg or greater. Reported adverse effects were similar between calcium and placebo phases and did not necessitate withdrawal of any patient from the trial. Treatment with 1000 mg/d of oral Ca2+ for 8 weeks represents a safe, well-tolerated, nonpharmacologic intervention that lowers blood pressure in selected patients with mild to moderate hypertension.", "Studies have provided conflicting results as to the protective role of calcium channel blockers (CCB) in cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function. Lacidipine is a dihydropyridine CCB that possesses antioxidative, anti-atherosclerotic, and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model.\n We conducted a multicenter prospective, randomized, placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy. The aim of this 2-year study was to assess the effects of lacidipine on graft function (plasma iohexol clearance), renal plasma flow, anastomotic arterial blood flow, deterioration of renal function, blood pressure, acute rejection, and hospitalization rate.\n A total of 118 recipients were available for intention-to-treat analysis on efficacy (lacidipine: n=59; placebo: n=59). Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance, was persistently better in lacidipine-treated patients from 1 year onwards (respectively, P<0.01 and P<0.05). Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients. Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60% (log-rank test: P=0.57). Study groups did not differ in acute rejection rate, trough blood cyclosporine concentrations, blood pressure, number of antihypertensive drugs, hospitalization rate, and adverse event rate.\n The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering.", "Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied.\n Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated.\n Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group.\n Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.\n Copyright 2005 S. Karger AG, Basel.", "Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin.\n 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat.\n 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment.\n The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.", "Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity. We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind, placebo-controlled trial. Patients were randomly assigned to placebo (n = 28) or verapamil (n = 32) at doses of 80 mg twice a day. There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms. Recipients randomized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up. Although cyclosporine doses were lower in the placebo group, the mean cyclosporine levels were equivalent in the two groups. Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study--1.7 mg/dL versus 1.4 mg/dL in the placebo group. Actual 1-year graft survival was 89% for the placebo recipients versus 91% in the verapamil-treatment group. When compared with placebo, the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels. Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed.", "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.", "Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium. A randomized, double-blind clinical trial was used to assess blood pressure response to orally administered potassium, 120 mEq/day, and to placebo in 101 adults with mild hypertension. Blood pressure was measured with a random-zero sphygmomanometer every 2 weeks of this 8-week trial. Systolic blood pressure in the potassium-treated group decreased by 6.4 +/- 13.7 (SD) mm Hg (p less than or equal to 0.025) compared with 0.11 +/- 13.0 mm Hg in the placebo-treated group (p = 0.96). Diastolic blood pressure in the potassium-treated group decreased by 4.1 +/- 8.3 mm Hg (p less than or equal to 0.05) compared with a 1.6 +/- 6.5 mm Hg decrease in placebo-treated subjects (p = 0.09). Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls. After correcting for baseline variation, blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients (p = 0.14 and 0.24, respectively). Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo. Compliance with the potassium regimen was 91.5% by pill count; only one subject discontinued treatment because of side effects. In conclusion, 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension. An antihypertensive effect of potassium cannot be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide.\n A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial.\n The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo.\n The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.", "Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate.\n A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability.\n At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group.\n Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.", "Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.\n Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.\n 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05).\n Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed." ]

[ "3305229", "8735733", "17023012", "8155220", "14556770" ]

[ "[Effectiveness of Alphastria cream in the prevention of pregnancy stretch marks (striae distensae). Results of a double-blind study].", "Stretching of the cervix and stripping of the membranes at term: a randomised controlled study.", "The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal: a common and potentially hazardous practice.", "Prevention of perineal trauma by perineal massage during pregnancy: a pilot study.", "Single-blind trial addressing the differential effects of two reflexology techniques versus rest, on ankle and foot oedema in late pregnancy." ]

[ "nan", "To determine whether routine antepartum stretching of the cervix and stripping of the membranes at term would shorten the length of pregnancies, and whether this correlated with cervical status and fetal and maternal parameters.\n A prospective, randomised, controlled study of 293 term gravidas, free of medical complications, divided into two groups: stretching/stripping, and non-stretching/stripping. Digital separation of the fetal membranes from the lower uterine segment, and cervical stretching, were performed during routine vaginal examination of the first group. In the second group, only routine vaginal examination was performed.\n Of 293 patients, 152 underwent a trial of stretching and stripping; 141 served as a control group. The mean interval (hours to delivery after the procedure) was 136 h (S.D. 10), compared to 161 h (S.D. 11) in the control group (P = 0.095; not significant), but with only a trend towards the shorter interval in the first group. When patients were matched according to weeks of gestation and fetal and maternal parameters, only those at 41 weeks' gestation or more had a significant reduction in the interval from the procedure to delivery (mean 91 h (S.D. 8) compared to mean 125 h (S.D. 10) in the control group; P < 0.007). This observation was independent of cervical status and other maternal or fetal parameters.\n Only patients > or = 41 weeks' gestation benefitted from stretching of the cervix and stripping of the fetal membranes. The effect was not dependent on the cervical status or other maternal and fetal parameters.", "Many women of childbearing age from sub-Saharan Africa use topical skin lighteners, some of which present a risk of toxic systemic effects. The goals of this study were to evaluate, in this environment, the frequency of this practice during pregnancy, as well as eventual consequences on pregnancy. Ninety-nine women from 6 to 9 months pregnant were randomly selected among those attending a standard maternal centre in Dakar for a prenatal visit. Investigations consisted of questions about the use of skin lighteners, a standard clinical examination, follow-up until delivery and a morning blood sample for plasma cortisol levels. Sixty-eight of the 99 selected women used skin lighteners during their current pregnancy, the main active ingredients being hydroquinone and highly potent steroids (used by 64 and 28 women, respectively). No difference in the main outcomes of pregnancy were found between skin-lightener users and the others; however, women using highly potent steroids, when compared with those who did not, had a statistically significant lower plasma cortisol level and a smaller placenta, and presented a higher rate of low-birth-weight infants. Skin lightening is a common practice during pregnancy in Dakar, and the use of steroids may result in consequences in the mother and her child.", "Although the performance of perineal massage by a woman or her partner during the last weeks of pregnancy may help to prevent perineal trauma at delivery, the technique has never been evaluated rigorously. This study examined the feasibility of a randomized, controlled trial, and more specifically assessed the participation rate, the acceptability of the intervention, and whether or not an attending physician could remain blind to participants' groups. The pilot study was a single-blinded, randomized, controlled trial. Nulliparous women, 32 to 34 weeks pregnant, were recruited from June 8 to July 31, 1992, at the offices of family physicians and obstetricians who practice at the Hôpital du Saint-Sacrement in Quebec City. Women assigned to the intervention group practiced daily 10-minute perineal massage and completed a diary, and those in the control group had standard care. Women and attending physicians completed a questionnaire about the aspect of blindness. Among the 174 women who delivered during the study period, 104 (59.8%) were approached by a midwife and 46 (26.4%) were randomized. Twenty (91.0%) of the 22 women in the massage group returned their perineal massage diaries. Based on the postpartum questionnaire, 20 women practiced the technique at least four times a week for three weeks or longer. No woman in the control group practiced massage. The attending physician was aware of the woman's group in only three instances (6.7%). Based on the results of this pilot study, a randomized, controlled trial to evaluate the efficacy of perineal massage in preventing perineal trauma at birth appears feasible.", "This single-blind randomised controlled trial explored the differential effects of two different foot reflexology techniques with a period of rest on oedema-relieving effects and symptom relief in healthy pregnant women with foot oedema. Fifty-five women in the third trimester were randomly assigned to one of the three groups: a period of rest, 'relaxing' reflexology techniques or a specific 'lymphatic' reflexology technique for 15 min with pre- and post-therapy ankle and foot circumference measurements and participant questionnaire. There was no statistically significant difference in the circumference measurements between the three groups; however, the lymphatic technique reflexology group mean circumference measurements were all decreased. A significant reduction in the women's symptom mean measurements in all groups (p<0.0001) was apparent. A 'perceived wellbeing' score revealed the lymphatic technique group (p<0.0001) significantly increased their wellbeing the most, followed closely by relaxing techniques (p<0.001) and then the control rest group (p<0.03). Lymphatic reflexology techniques, relaxing reflexology techniques and a period of rest had a non-significant oedema-relieving effect. From the women's viewpoint, lymphatic reflexology was the preferred therapy with significant increase in symptom relief." ]

[ "12100779", "9602398", "3711252", "594708", "7112052", "15653255", "8124120", "10074017", "7488463", "2495053", "8182811", "16622437", "3903732", "10356008" ]

[ "General health screenings to improve cardiovascular risk profiles: a randomized controlled trial in general practice with 5-year follow-up.", "Effects of an assessment of needs for medical and social services on long-term mortality: a randomized controlled study.", "Multiphasic Health Checkup Evaluation: a 16-year follow-up.", "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 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.", "Long-term efficacy of a checklist to improve patient education in cardiology.", "Effectiveness of health checks conducted by nurses in primary care: results of the OXCHECK study after one year. Imperial Cancer Research Fund OXCHECK Study Group.", "Randomised controlled trial of follow up care in general practice of patients with myocardial infarction and angina: final results of the Southampton heart integrated care project (SHIP). The SHIP Collaborative Group.", "Mortality in participants and non-participants of a multifactorial prevention study of cardiovascular diseases: a 28 year follow up of the Helsinki Businessmen Study.", "Using nurses for preventive activities with computer assisted follow up: a randomised controlled trial.", "Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators.", "General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled trial.", "WHO European Collaborative Trial of multifactorial prevention of coronary heart disease.", "Effect of postal prompts to patients and general practitioners on the quality of primary care after a coronary event (POST): randomised controlled trial." ]

[ "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.", "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.", "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.", "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.", "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.", "In a randomised controlled trial a Frequently Asked Questions (FAQ) checklist intended to prepare coronary artery disease (CAD) outpatients for a medical check-up visit at the cardiologist was evaluated. The checklist was mailed to patients in preparation to their visits after 1, 4 and 10 months following patients' discharge from hospitalisation for CAD. It was hypothesised that the intervention would result in lower state anxiety, better patient-doctor communication, more knowledge of CAD and greater patient satisfaction, while it would not result in longer visits. Repeated measurements analyses of covariance showed that experimental patients (N = 46) were less anxious before the first visit. This visit was shorter than in the controls, though the third visit was longer. Control patients (N = 59) showed more CAD knowledge than experimental patients at the first and third visit. Experimental patients found the checklist useful, though its value diminished at subsequent visits. Using the checklist thus decreased anxiety prior to the first visit and the duration of that visit, while negatively affecting knowledge. No conclusions about long-term effects could be drawn, due to the likelihood of type II and type III errors. Process evaluation indicated that the approach used is not sufficiently stimulating for patients to use as a preparation to every visit.", "To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice.\n Randomised controlled trial.\n Five urban general practices in Bedfordshire.\n 2136 patients receiving an initial health check in 1989-91 and scheduled to be re-examined one year later in 1990-2 (intervention group); 3988 patients receiving an initial health check in 1990-2 (control group). All patients were aged 35-64 years at recruitment in 1989.\n Serum total cholesterol concentration, blood pressure, body mass index, confirmed smoking cessation.\n Mean serum total cholesterol was 2.3% lower in the intervention group than in the controls (difference 0.14 mmol/l (95% confidence interval 0.08 to 0.20)); the difference was greater in women (3.2%, P < 0.0001) than men (1.0%, P = 0.18). There was no significant difference in smoking prevalence, quit rates, or body mass index. Systolic and diastolic blood pressure were 2.5% and 2.4% lower respectively in the intervention group. The proportion of patients with diastolic blood pressure > or = 100 mm Hg was 2.6% (55/2131) in the intervention group and 3.4% (137/3987) in the controls (difference 0.9% (0.0 to 1.7)); the proportion with total cholesterol concentration > or = 8 mmol/l 4.8% (100/2068) and 7.6% (295/3905) (difference 2.7% (1.5 to 4.0)); and that with body mass index > or = 30 12.4% (264/2125) and 14.0% (559/3984) (difference 1.6% (-0.2 to 3.4)).\n General health checks by nurses are ineffective in helping smokers to stop smoking, but they help patients to modify their diet and total cholesterol concentration. The public health importance of this dietary change depends on whether it is sustained.", "To assess the effectiveness of a programme to coordinate and support follow up care in general practice after a hospital diagnosis of myocardial infarction or angina.\n Randomised controlled trial; stratified random allocation of practices to intervention and control groups.\n All 67 practices in Southampton and south west Hampshire, England.\n 597 adult patients (422 with myocardial infarction and 175 with a new diagnosis of angina) who were recruited during hospital admission or attendance at a chest pain clinic between April 1995 and September 1996.\n Programme to coordinate preventive care led by specialist liaison nurses which sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow up.\n Serum total cholesterol concentration, blood pressure, distance walked in 6 minutes, confirmed smoking cessation, and body mass index measured at 1 year follow up.\n Of 559 surviving patients at 1 year, 502 (90%) were followed up. There was no significant difference between the intervention and control groups in smoking (cotinine validated quit rate 19% v 20%), lipid concentrations (serum total cholesterol 5.80 v 5.93 mmol/l), blood pressure (diastolic pressure 84 v 85 mm Hg), or fitness (distance walked in 6 minutes 443 v 433 m). Body mass index was slightly lower in the intervention group (27.4 v 28.2; P=0.08).\n Although the programme was effective in promoting follow up in general practice, it did not improve health outcome. Simply coordinating and supporting existing NHS care is insufficient. Ischaemic heart disease is a chronic condition which requires the same systematic approach to secondary prevention applied in other chronic conditions such as diabetes mellitus.", "To investigate pretrial risk factors and long term mortality (1964-1992) in participants and non-participants of a multifactorial primary prevention trial.\n A prospective study among 3313 initially healthy businessmen. During the 1960s (1964 onwards), 3490 healthy male business executives born between 1919 and 1934 participated in voluntary health checks at the Institute of Occupational Health in Helsinki. From that period cardiovascular disease (CVD) risk factors were available in 3313 men. In the beginning of the 1970s these men were invited to join a multifactorial primary prevention trial of CVD. Six groups were formed: (I) healthy participants in a high risk intervention group (n = 612), and (II) their randomised control group (n = 610); (III) a non-participant low risk group (n = 593); (IV) an excluded group with signs of CVD (n = 563); (V) a refused group (n = 867); and (VI) dead (n = 68). Groups I and II participated in the five year prevention trial which started in 1974. Other groups were followed up through registers, with no personal contact.\n Cardiovascular risk factors during the 1960s. Mortality follow up using national registers up to 31 December, 1992.\n Baseline risk factors were lowest in the low risk group, highest in the excluded group, intermediate and comparable in other groups. Eighteen-year (1974-1992) mortality (per 1000) was 79.3, 106.6, 155.2, 179.9, and 259.3 in the low risk, control, intervention, refused, and excluded groups, respectively (P < 0.001). In the whole population of 3313 men, the 28-year (1964-1992) total (n = 577) and coronary deaths (n = 199) were significantly predicted by smoking, blood pressure, and cholesterol; cancer deaths (n = 163) by smoking only; and violent deaths (n = 83) by none of the risk factors. One-hour postload glucose was significantly associated with total mortality in the intervention group only. When the intervention and control groups were included in the same model, the effect of group on total mortality tended to be dependent on the 1 h blood glucose value (P = 0.06 for the group by 1 h glucose interaction term).\n The traditional risk factors (smoking, blood pressure, and cholesterol) are significantly associated with 28-year mortality in this high social class population with previous health education. Conversely, a \"clustering\" of low risk factors predicted low total, coronary, and cancer mortality. The findings on 1 h blood glucose suggest that factors related to glucose tolerance explain in part the excess mortality in the intervention group compared with the control group.", "To assess whether an organised programme of prevention including the use of a health promotion nurse noticeably improved recording and follow up of cardiovascular risk factors and cervical smears in a general practice that had access to computerised cell and recall.\n Randomised controlled trial.\n General practice in inner London.\n All 3206 men and women aged 30-64 registered with the practice.\n The intervention group had their risk factors ascertained and followed up by the health promotion nurse and the general practitioner, whereas those in the control group were managed by the general practitioner alone.\n Recording and follow up of blood pressure and cervical smears after three years. Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations were also examined. MEASUREMENTS and\n When the trial was stopped after two years the measurements of blood pressure in the preceding five years were 93% (1511/1620) v 73% (1160/1586) (95% confidence interval for difference 17.5 to 22.7%) for intervention and control groups respectively. For patients with hypertension the figures were 97% (104/107) v 69% (80/116) (18.2 to 38.2%). For women the proportion who had had a cervical smear in the preceding three years were 76% (606/799) v 49% (392/806) (22.5 to 31.9%). Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations was also higher in the intervention group compared with the control group.\n An organised programme, which includes a nurse with specific responsibility for adult prevention, is likely to make an important contribution to recording of risk factors and follow up of those patients with known risks.", "To assess prospectively the impact on survival and health-related quality of life of two follow-up protocols in patients with early breast cancer.\n Randomized controlled clinical trial.\n Multicenter study involving 26 general hospitals in Italy.\n A consecutive sample of 1320 women younger than 70 years with stage I, II, and III unilateral primary breast cancer.\n Patients were randomly assigned to an intensive surveillance, which included physician visits and performance of bone scan, liver echography, chest roentgenography, and laboratory tests at predefined intervals (n = 655), or to a control regimen (n = 665), in which patients were seen by their physicians at the same frequency but only clinically indicated tests were performed. Both groups received a yearly mammogram aimed at detecting contralateral breast cancer.\n Primary end points were overall survival and health-related quality of life.\n Compliance to the two follow-up protocols was more than 80%. At a median follow-up of 71 months, no difference was apparent in overall survival with 132 deaths (20%) in the intensive group and 122 deaths (18%) in the control group. No significant differences were apparent in time to detection of recurrence between the two groups. Measurements of health-related quality of life (ie, overall health and quality-of-life perception, emotional well-being, body image, social functioning, symptoms, and satisfaction with care) at 6, 12, 24, and 60 months of follow-up did not show differences by type of care received.\n Results of this trial support the view that a protocol of frequent laboratory tests and roentgenography after primary treatment for breast cancer does not improve survival or influence health-related quality of life. Routine use of these tests should be discouraged.", "This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4-4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5-1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3-1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes, although patterns of investigation vary.", "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.", "To determine whether postal prompts to patients who have survived an acute coronary event and to their general practitioners improve secondary prevention of coronary heart disease.\n Randomised controlled trial. Setting: 52 general practices in east London, 44 of which had received facilitation of local guidelines for coronary heart disease. Participants: 328 patients admitted to hospital for myocardial infarction or unstable angina. Interventions: Postal prompts sent 2 weeks and 3 months after discharge from hospital. The prompts contained recommendations for lowering the risk of another coronary event, including changes to lifestyle, drug treatment, and making an appointment to discuss these issues with the general practitioner or practice nurse.\n Proportion of patients in whom serum cholesterol concentrations were measured; proportion of patients prescribed beta blockers (6 months after discharge); and proportion of patients prescribed cholesterol lowering drugs (1 year after discharge).\n Prescribing of beta bockers (odds ratio 1.7, 95% confidence interval 0.8 to 3.0, P>0.05) and cholesterol lowering drugs (1.7, 0. 8 to 3.4, P>0.05) did not differ between intervention and control groups. A higher proportion of patients in the intervention group (64%) than in the control group (38%) had their serum cholesterol concentrations measured (2.9, 1.5 to 5.5, P<0.001). Secondary outcomes were significantly improved for consultations for coronary heart disease, the recording of risk factors, and advice given. There were no significant differences in patients' self reported changes to lifestyle or to the belief that it is possible to modify the risk of another coronary event.\n Postal prompts to patients who had had acute coronary events and to their general practitioners in a locality where guidelines for coronary heart disease had been disseminated did not improve prescribing of effective drugs for secondary prevention or self reported changes to lifestyle. The prompts did increase consultation rates related to coronary heart disease and the recording of risk factors in the practices. Effective secondary prevention of coronary heart disease requires more than postal prompts and the dissemination of guidelines." ]

[ "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." ]

[ "12612277", "23119911", "18179756", "17533178", "7862473", "6507997" ]

[ "Frequency of surgery among children who have adenotonsillar hypertrophy and improve after treatment with nasal beclomethasone.", "Chronic adenoid hypertrophy in children - is steroid nasal spray beneficial?", "Intranasal flunisolide treatment in children with adenoidal hypertrophy.", "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.", "Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction with aqueous nasal beclomethasone.", "Effect of an intranasally administered corticosteroid (budesonide) on nasal obstruction, mouth breathing, and asthma." ]

[ "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.", "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.", "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.", "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.", "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.", "The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma." ]

[ "15321453", "10730733", "10992845", "9893537", "11454372" ]

[ "A randomised controlled trial of fluid pre-loading before low dose epidural analgesia for labour.", "Comparison of combined spinal-epidural and low dose epidural for labour analgesia.", "Randomized study of intravenous fluid preload before epidural analgesia during labour.", "Regional analgesia in early active labour: combined spinal epidural vs. epidural.", "Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial." ]

[ "Preloading with fluid is recommended before regional block in labour. Low dose epidurals may produce less haemodynamic disturbance than traditional stronger solutions of local anaesthetics. Our aim was to compare the incidence of hypotension in normal labouring women who received a low dose epidural (0.1% bupivacaine 15 mL with fentanyl 2 microg microg.mL(-1)) with and without an i.v. crystalloid preload. Women with normal labours were randomised to the intervention group: no i.v. crystalloid preload (n = 85) and the control group: 7 mL mL.kg(-1) i.v. crystalloid solution before epidural injection (n = 83). Mean arterial pressure was recorded every 5 min for 30 min. There was no difference between the groups in mean decrease in mean arterial pressure and similar proportions of women showed falls in mean arterial pressure of 20% or greater (13% vs. 11%, risk ratio 1.2, 95% CI 0.54 to 2.8, P = 0.6). Blinded analysis by independent obstetricians revealed no differences in the fetal heart rate abnormalities (20% vs. 15%, risk ratio 1.3, 95% CI 0.67 to 2.7). A scientifically valid conclusion whether preloading is useful cannot be drawn from this study. This study suggests that about 350 participants in each group would be necessary to exclude a type 2 error in a future study.", "To compare the combined spinal-epidural (CSE) technique with the epidural technique with regard to time to initiate and manage, motor block, onset of analgesia and satisfaction during labour.\n Upon requesting analgesia, 50 healthy term parturients were randomized in a prospective, double-blind fashion to receive either CSE analgesia or lumbar epidural analgesia in the labour floor of a university hospital at an academic medical centre. The epidural group (n = 24) received bupivacaine 0.0625%-fentanyl 0.0002% with 0.05 ml in 10 ml local anesthetic sodium bicarbonate 8.4% and epinephrine 1:200,000. The CSE group (n = 26) received intrathecal 25 microg fentanyl and 2.5 mg bupivacaine. Additional analgesia was provided upon maternal request.\n There were no differences (P>0.05) in time to perform either technique, motor blockade, or parturient satisfaction or in the number of times that the anesthesiologist was called to perform any intervention. Although the first sign of analgesia was not different between the two groups, the onset of complete analgesia was more rapid with the CSE technique (Visual Analogue Pain Score (VAPS) at five minutes < three: 26/26 vs. 17/24, P+/-0.001).\n Although epidural analgesia with a low concentration of local anesthetic and opioid mixture takes longer to produce complete analgesia, it is a satisfactory alternative to CSE.", "We performed a randomized controlled trial of the effect of intravenous fluid preload on maternal hypotension and fetal heart rate (FHR) changes in labour after the first epidural injection. Group 1 (49 women) received 1 litre of crystalloid preload. Group 2 (46 women) received no preload. No statistically significant difference was shown between the two groups for either of the outcomes. Hypotension was found in three women in group 1 and five in group 2 (P = 0.4). Deterioration in FHR pattern was found in four women in group 1 and 11 in group 2 (P = 0.08). This study has not shown a significant increase in the incidence of hypotension when intravenous preload is omitted before epidural analgesia using a low concentration of bupivacaine during labour. Because of the clinical importance of the difference in the rate of FHR deterioration between the two groups, we continue to administer preload for high-risk cases.", "We randomly allocated 93 women in early active labour and requesting epidural analgesia to receive either epidural (n = 48) or combined spinal-epidural analgesia (n = 45). For epidural analgesia 15 ml of bupivacaine 0.1% with 75 micrograms of fentanyl were injected into the epidural space. For combined spinal-epidural analgesia 1 ml of bupivacaine 0.25% with 25 micrograms of fentanyl were injected into the subarachnoid space. For both groups subsequent top-ups of 10 ml of bupivacaine 0.1% with fentanyl 20 micrograms were given using a lightweight patient-controlled epidural analgesia (PCEA) pump with a lockout time of 30 min. We assessed analgesia and the degree of motor blockade and found no significant differences in pain or maternal satisfaction scores between the two groups. The time to first top-up was significantly longer in the epidural group than in the CSE group (p = 0.01). The combined spinal-epidural group had significantly greater motor blockade at 30 min than the epidural group (p = 0.01), but there was no difference after this. The PCEA machine failed completely twice and temporarily many times. We conclude that the combined spinal-epidural technique confers no advantages in early active labour. Also, a lightweight PCEA pump needs to be more reliable before we can recommend its use.", "Epidural analgesia is the most effective labour pain relief but is associated with increased rates of instrumental vaginal delivery and other effects, which might be related to the poor motor function associated with traditional epidural. New techniques that preserve motor function could reduce obstetric intervention. We did a randomised controlled trial to compare low-dose combined spinal epidural and low-dose infusion (mobile) techniques with traditional epidural technique.\n Between Feb 1, 1999, and April 30, 2000, we randomly assigned 1054 nulliparous women requesting epidural pain relief to traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose infusion epidural (n=350). Primary outcome was mode of delivery, and secondary outcomes were progress of labour, efficacy of procedure, and effect on neonates. We obtained data during labour and interviewed women postnatally.\n The normal vaginal delivery rate was 35.1% in the traditional epidural group, 42.7% in the low-dose combined spinal group (odds ratio 1.38 [95% CI 1.01-1.89]; p=0.04); and 42.9% in the low-dose infusion group (1.39 [1.01-1.90]; p=0.04). These differences were accounted for by a reduction in instrumental vaginal delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low-dose technique. High-level resuscitation was more frequent in the low-dose infusion group.\n The use of low-dose epidural techniques for labour analgesia has benefits for delivery outcome. Continued routine use of traditional epidurals might not be justified." ]

[ "2707458", "8299789", "12070543", "12413984", "16543255" ]

[ "Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin.", "Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.", "The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome.", "Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial.", "Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study." ]

[ "A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic.", "To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles.\n Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study.\n Tertiary academic medical center.\n Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles.\n Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle).\n If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.", "To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.\n This study was carried out at King Hussein Medical Center, Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12). During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to 200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was indicative of ovulation.\n A statistically significant increase in the rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%, p<0.05) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls. Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group.\n Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates, and decreases the occurrence of ovarian hyperstimulation syndrome.", "To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels.\n Prospective, double-blind, placebo-controlled, randomized study.\n Referral university hospitals.\n Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC.\n The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo.\n Follicular development, hormonal status, ovulation rate, pregnancy rate.\n Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant.\n Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention.", "The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation.\n Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised.\n There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism.\n Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR." ]

[ "12694632", "15108041", "11730399", "15190995", "15066200", "19366977", "9746022", "11490051", "16084254", "17298190", "12928469", "12816022", "11298072", "17175680", "15451835", "15868015", "21350242", "9616530", "16507343", "19775439", "7050440", "20122041", "14729297", "17101295", "10980076", "20679560", "9740569", "9330945", "19091806", "17473138" ]

[ "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.", "Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.", "A randomized controlled trial of a specific reminiscence approach to promote the well-being of nursing home residents with dementia.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Customized feedback to patients and providers failed to improve safety or quality of diabetes care: a randomized trial.", "Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?", "Randomized clinical trial of a quality improvement intervention in nursing homes.", "Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.", "Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure.", "Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?", "Improving primary care in rural Alabama with a pharmacy initiative.", "Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.", "Effects of a brief computer-assisted diabetes self-management intervention on dietary, biological and quality-of-life outcomes.", "Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research.", "Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa.", "A randomized trial of effects of health risk appraisal combined with group sessions or home visits on preventive behaviors in older adults.", "One-year economic evaluation of intensive vs conventional patient education and supervision for self-management of new asthmatic patients.", "A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group.", "Effects of a restraint minimization program on staff knowledge, attitudes, and practice: a cluster randomized trial.", "Promoting patient participation in consultations: a randomised controlled trial to evaluate the effectiveness of three patient-focused interventions.", "Association of industry sponsorship to published outcomes in gastrointestinal clinical research.", "Improving doctors' prescribing behaviour through reflection on guidelines and prescription feedback: a randomised controlled study.", "Outcome reporting among drug trials registered in ClinicalTrials.gov.", "A multidisciplinary approach for improving services in primary care: randomised controlled trial of screening for haemoglobin disorders.", "A comparison of behavioral and educational interventions for fibromyalgia.", "Conducting a randomized clinical trial of an psychological intervention for parents/caregivers of children with cancer shortly after diagnosis.", "Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not." ]

[ "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).\n Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).\n A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group > chemotherapy group > control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.\n The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).", "To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.", "To date, no firm conclusions can be reached regarding the effectiveness of reminiscence for dementia. Researchers have emphasized that there is an urgent need for more systematic research in the area.\n A single-blinded, parallel-groups (one intervention, one comparison, and one no-intervention group) randomized controlled trial (RCT) was adopted to investigate whether a specific reminiscence program leads to higher levels of psychosocial well-being in nursing home residents with dementia. The intervention adopted a life-story approach, while the comparison group provided friendly discussions to control for any changes in outcome as a result of social contacts and attention. The Social Engagement Scale (SES) and Well-being/Ill-being Scale (WIB) were the outcome measures used. The outcomes of the groups were examined with reference to the baseline (T0), immediately (T1), and six weeks (T2) after intervention. The final sample had 101 subjects (control group: n=30; comparison group: n=35; intervention group: n = 36). Using multivariate analysis with repeated measures, no significant differences in outcome were found between groups at either T1 or T2. Wilcoxon signed rank tests were performed for each group comparing outcomes between T1 and T0, T2 and T1, and T2 and T0. Significant differences were observed in the intervention group when comparing T1 and T0 WIB (p = .014), but not for the other groups.\n Although the intervention did not lead to significant differences between the three groups over time, there was a significant improvement in psychosocial well-being for the intervention group.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "To assess whether providing customized clinical information to patients and physicians improves safety or quality of diabetes care.\n Study subjects included 123 primary care physicians and 3,703 eligible adult diabetic patients with elevated A1C or LDL cholesterol, who were randomly assigned to receive customized feedback of clinical information as follows: 1) patient only, 2) physician only, 3) both the patient and physician, or 4) neither patient nor physician. In the intervention groups, patients received customized mailed information or physicians received printed, prioritized lists of patients with recommended clinical actions and performance feedback. Hierarchical models were used to accommodate group random assignment.\n Study interventions did not improve A1C test ordering (P = 0.35) and negatively affected LDL cholesterol test ordering (P < 0.001) in the 12 months postintervention. Interventions had no effect on LDL cholesterol values (P = 0.64), which improved in all groups over time. Interventions had a borderline unfavorable effect on A1C values among those with baseline A1C >or=7% (P = 0.10) and an unfavorable effect on A1C values among those with baseline A1C >or=8% (P < 0.01). Interventions did not reduce risky prescribing events or increase treatment intensification. Time to next visit was longer in all intervention groups compared with that for the control group (P < 0.05).\n Providing customized decision support to physicians and/or patients did not improve quality or safety of diabetes care and worsened A1C control in patients with baseline A1C >or=8%. Future researchers should consider providing point-of-care decision support with redesign of office systems and/or incentives to increase appropriate actions in response to decision-support information.", "Few meta-analyses of randomised trials assess the quality of the studies included. Yet there is increasing evidence that trial quality can affect estimates of intervention efficacy. We investigated whether different methods of quality assessment provide different estimates of intervention efficacy evaluated in randomised controlled trials (RCTs).\n We randomly selected 11 meta-analyses that involved 127 RCTs on the efficacy of interventions used for circulatory and digestive diseases, mental health, and pregnancy and childbirth. We replicated all the meta-analyses using published data from the primary studies. The quality of reporting of all 127 clinical trials was assessed by means of component and scale approaches. To explore the effects of quality on the quantitative results, we examined the effects of different methods of incorporating quality scores (sensitivity analysis and quality weights) on the results of the meta-analyses.\n The quality of trials was low. Masked assessments provided significantly higher scores than unmasked assessments (mean 2.74 [SD 1.10] vs 2.55 [1.20]). Low-quality trials (score < or = 2), compared with high-quality trials (score > 2), were associated with an increased estimate of benefit of 34% (ratio of odds ratios [ROR] 0.66 [95% CI 0.52-0.83]). Trials that used inadequate allocation concealment, compared with those that used adequate methods, were also associated with an increased estimate of benefit (37%; ROR=0.63 [0.45-0.88]). The average treatment benefit was 39% (odds ratio [OR] 0.61 [0.57-0.65]) for all trials, 52% (OR 0.48 [0.43-0.54]) for low-quality trials, and 29% (OR 0.71 [0.65-0.77]) for high-quality trials. Use of all the trial scores as quality weights reduced the effects to 35% (OR 0.65 [0.59-0.71]) and resulted in the least statistical heterogeneity.\n Studies of low methodological quality in which the estimate of quality is incorporated into the meta-analyses can alter the interpretation of the benefit of intervention, whether a scale or component approach is used in the assessment of trial quality.", "The purpose of the study was to determine if simply providing nursing facilities with comparative quality performance information and education about quality improvement would improve clinical practices and subsequently improve resident outcomes, or if a stronger intervention, expert clinical consultation with nursing facility staff, is needed.\n Nursing facilities (n = 113) were randomly assigned to one of three groups: workshop and feedback reports only, workshop and feedback reports with clinical consultation, and control. Minimum Data Set (MDS) Quality Indicator (QI) feedback reports were prepared and sent quarterly to each facility in intervention groups for a year. Clinical consultation by a gerontological clinical nurse specialist (GCNS) was offered to those in the second group.\n With the exception of MDS QI 27 (little or no activity), no significant differences in resident assessment measures were detected between the groups of facilities. However, outcomes of residents in nursing homes that actually took advantage of the clinical consultation of the GCNS demonstrated trends in improvements in QIs measuring falls, behavioral symptoms, little or no activity, and pressure ulcers (overall and for low-risk residents).\n Simply providing comparative performance feedback is not enough to improve resident outcomes. It appears that only those nursing homes that sought the additional intensive support of the GCNS were able to effect enough change in clinical practice to improve resident outcomes significantly.", "We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.\n 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.\n 132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.\n Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.", "To assess the efficacy of a multifactorial educational intervention carried out by a pharmacist in patients with heart failure (HF).\n A randomized, prospective, open clinical trial in patients admitted for HF. The patients assigned to the intervention group received information about the disease, drug therapy, diet education, and active telephone follow-up. Visits were completed at 2, 6, and 12 months. Hospital re-admissions, days of hospital stay, treatment compliance, satisfaction with the care received, and quality of life (EuroQol) were evaluated; a financial study was conducted in order to assess the possible impact of the program. The intervention was performed by the pharmacy department in coordination with the cardiology unit.\n 134 patients were included, with a mean age of 75 years and a low educational level. The patients of the intervention group had a higher level of treatment compliance than the patients in the control group. At 12 months of follow-up, 32.9% fewer patients in the intervention group were admitted again vs. the control group. The mean days of hospital stay per patient in the control group were 9.6 (SD=18.5) vs. 5.9 (SD=14.1) in the intervention group. No differences were recorded in quality of life, but the intervention group had a higher score in the satisfaction scale at two months [9.0 (SD=1.3) versus 8.2 (SD=1.8) p=0.026]. Upon adjusting a Cox survival model with the ejection fraction, the patients in the intervention group had a lower risk of re-admission (Hazard ratio 0.56; 95% CI: 0.32-0.97). The financial analysis evidenced savings in hospital costs of euro 578 per patient that were favorable to the intervention group.\n Postdischarge pharmaceutical care allows for reducing the number of new admissions in patients with heart failure, the total days of hospital stay, and improves treatment compliance without increasing the costs of care.", "Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.\n To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.\n Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).\n Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.\n The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.\n Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.", "The effect of pharmaceutical care on the prevention, detection, and resolution of medication-related problems in high-risk patients in a rural community was studied. Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were randomly assigned to a control group or an intervention group. The control group received standard medical care, and the intervention group received pharmaceutical care, including a medical record review, a medication history review, pharmacotherapeutic evaluation, and patient medication education and monitoring over a one-year period. A total of 69 patients completed the study (33 in the intervention group and 36 in the control group). The percentage of patients responding to hypertension, diabetes, dyslipidemia, and anticoagulation therapy increased significantly in the intervention group and declined in the control group. Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group. There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures. Medication compliance scores improved in the intervention group but not in the control group. Medication knowledge increased in the intervention group and decreased in the control group. Pharmaceutical care in a rural, community-based setting appeared to reduce inappropriate prescribing, enhance disease management, and improve medication compliance and knowledge without adversely affecting health-related quality of life.", "To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.", "There is a need for practical, efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss. The objective of this study was to evaluate such a computer-assisted intervention.\n Type 2 diabetes primary care patients (n=335) from fee-for-service and health maintenance organization settings were randomized to social cognitive theory-based tailored self-management (TSM) or computer-aided enhanced usual care (UC). Intervention consisted of computer-assisted self-management assessment and feedback, tailored goal-setting, barrier identification, and problem-solving, followed by health counsellor interaction and follow-up calls. Outcomes were changes in dietary behaviours (fat and fruit/vegetable intake), haemoglobin Alc (HbA1c), lipids, weight, quality of life, and depression.\n TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up. Among patients having elevated levels of HbA1c, lipids or depression at baseline, there were consistent directional trends favouring intervention, but these differences did not reach significance. The intervention proved feasible and was implemented successfully by a variety of staff.\n This relatively low-intensity intervention appealed to a large, generally representative sample of patients, was well implemented, and produced improvement in targeted behaviours. Implications of this practical clinical trial for dissemination are discussed.", "The reporting of outcomes within published randomized trials has previously been shown to be incomplete, biased and inconsistent with study protocols. We sought to determine whether outcome reporting bias would be present in a cohort of government-funded trials subjected to rigorous peer review.\n We compared protocols for randomized trials approved for funding by the Canadian Institutes of Health Research (formerly the Medical Research Council of Canada) from 1990 to 1998 with subsequent reports of the trials identified in journal publications. Characteristics of reported and unreported outcomes were recorded from the protocols and publications. Incompletely reported outcomes were defined as those with insufficient data provided in publications for inclusion in meta-analyses. An overall odds ratio measuring the association between completeness of reporting and statistical significance was calculated stratified by trial. Finally, primary outcomes specified in trial protocols were compared with those reported in publications.\n We identified 48 trials with 68 publications and 1402 outcomes. The median number of participants per trial was 299, and 44% of the trials were published in general medical journals. A median of 31% (10th-90th percentile range 5%-67%) of outcomes measured to assess the efficacy of an intervention (efficacy outcomes) and 59% (0%-100%) of those measured to assess the harm of an intervention (harm outcomes) per trial were incompletely reported. Statistically significant efficacy outcomes had a higher odds than nonsignificant efficacy outcomes of being fully reported (odds ratio 2.7; 95% confidence interval 1.5-5.0). Primary outcomes differed between protocols and publications for 40% of the trials.\n Selective reporting of outcomes frequently occurs in publications of high-quality government-funded trials.", "To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%.\n A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment.\n The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation.\n This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required.", "To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany.\n Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse).\n Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement.\n HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior.", "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.", "Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.", "To evaluate the effects of a restraint minimization education program on staff knowledge and attitudes and use of physical restraints.\n Cluster-randomized controlled trial with nursing units as the basis for randomization.\n Forty group dwelling units for people with dementia.\n At baseline, there were 184 staff and 191 residents in the intervention group and 162 staff and 162 residents in the control group. At the 6-month follow-up, there were 156 staff and 185 residents (36 newly admitted) in the intervention group and 133 staff and 165 residents (26 newly admitted) in the control group.\n A 6-month education program for all nursing staff.\n Staff knowledge and attitudes and physical restraint use were measured before and after the education program.\n In the intervention group, staff knowledge about and attitudes toward restraint use changed, and the overall use of physical restraints decreased. A comparison including only residents present during the whole study period showed that the level of use was similar between the groups at baseline, whereas it was significantly lower in the intervention group at follow-up. Adjusted analyses showed that the odds of being restrained at follow-up were lower in the intervention group than in the control group. There was no significant change in the number of falls or use of psychoactive medication.\n The results indicate that staff education can increase knowledge, change attitudes, and reduce the use of physical restraints without any change in the incidence of falls or use of psychoactive drugs.", "The aim of this experimental study was to evaluate the effectiveness of three patient-focused interventions designed to increase patient question asking in clinical consultations. Patients were randomly allocated to one of five conditions to receive either one of three interventions or to serve as an attention control group or a control group. The primary outcome measure was question asking by the patient of their physician. Participants in the intervention groups did not ask more questions than participants in the control groups. Immediately after the consultation participants in the intervention groups had higher levels of self-efficacy in asking questions. Three months after the index visit patients in the intervention groups were significantly more likely to be satisfied to some degree than patients in the control group. There was no difference in diabetic control. These results suggest that simple brief patient-focused interventions do not change patient behaviour in medical outpatient consultations.", "Recent years have seen an increase in industry sponsorship of clinical trials throughout medicine. We conducted a study to evaluate the association of industry sponsorship to published outcomes in gastrointestinal (GI) clinical research. Our aims were (1) to evaluate the trends in the source of funding for GI clinical research during the period from 1992 to 2002-2003, (2) to determine whether the source of study funding predicted the likelihood that a study would publish results that favor the drug or device being tested, and (3) to determine whether differences exist in the methodologic quality of the investigational study methods used in studies funded by private industry versus other sources.\n We selected all clinical studies evaluating a drug or device from 4 prominent GI journals (Gastroenterology, The American Journal of Gastroenterology, Hepatology, and Gastrointestinal Endoscopy). All studies were abstracted by using a standardized data abstraction form. We evaluated the trends in funding source for studies published during the years 1992, 2002, and 2003. All selected studies were scored for methodologic quality by using a previously validated scoring system. The percentage of studies that reported outcomes that favored the device or drug being tested against the standard therapy or placebo was determined for each funding source. A funnel plot was constructed to assess for the presence of negative publication bias.\n A total of 6326 studies were reviewed. For the 1992 trend data, 1860 studies were reviewed, and 135 were selected for inclusion in the study. Ninety-five studies were studies involving the investigation of drugs, and 40 studies involved the testing of a device. For the 2002-2003 data 4466 studies were reviewed, and 315 were selected for inclusion in the study. Two hundred twenty-two studies were clinical trials involving the investigation of drugs, and 93 were clinical trials involving devices. In comparing 1992 to 2002, the percentage of studies funded by industry sources more than doubled from 10% to greater than 28% of the total studies assessed. There was an associated decline in the proportion of studies with funding from non-industry sources during this period (62% to less than 48%). The percentage of studies that did not disclose a funding source fell modestly from 28% to 24%. We found that 86% of studies funded by private industry reported a result favorable to the study drug or device, and 83% of studies funded by academic sources reported a result favorable to the study drug or device (P=.572). On average, studies funded by private industry had a higher methodology score than studies funded by traditional academic sources (75 of 100 vs 65 of 100; P=.005). Analysis of the funnel plot did not reveal evidence of bias against the publication of small studies with insignificant results.\n The proportion of research funded by industry has more than doubled during the last decade and currently comprises almost half of the funding for GI clinical research. Industry-sponsored studies are, on average, of superior methodologic quality to studies funded by other sources. Industry-sponsored studies in leading GI journals were no more likely than other studies to publish results that favored the study sponsor, although an extremely high percentage of all studies in these journals reported positive results. There has been only a modest decline in studies not acknowledging a funding source.", "It is difficult to put research findings into clinical practice by either guidelines or prescription feedback.\n To study the effect on the quality of prescribing by a combined intervention of providing individual feedback and deriving quality criteria using guideline recommendations in peer review groups.\n 199 general practitioners in 32 groups were randomised to participate in peer review meetings related to either asthma or urinary tract infections. The dispensing by the participating doctors of antiasthmatic drugs and antibiotics during the year before the intervention period provided the basis for prescription feedback. The intervention feedback was designed to describe the treatment given in relation to recommendations in the national guidelines. In each group the doctors agreed on quality criteria for their own treatment of the corresponding diseases based on these recommendations. Comparison of their prescription feedback with their own quality criteria gave each doctor the proportion of acceptable and unacceptable treatments.\n Difference in the prescribing behaviour between the year before and the year after the intervention.\n Before intervention the mean proportions of acceptably treated asthma patients in the asthma group and urinary tract infection (control) group were 28% and 27%, respectively. The mean proportion of acceptably treated patients in the asthma group was increased by 6% relative to the control group; this difference was statistically significant. The mean proportions of acceptable treatments of urinary tract infection before intervention in the urinary tract infection group and asthma (control) group were 12% for both groups which increased by 13% in the urinary tract infection group relative to the control group. Relative to the mean pre-intervention values this represented an improvement in treatment of 21% in the asthma group and 108% in the urinary tract infection group.\n Deriving quality criteria of prescribing by discussing guideline recommendations gave the doctors a basis for judging their treatment of individual patients as acceptable or unacceptable. Presented with feedback on their own prescribing, they learned what they did right and wrong. This provided a foundation for improvement and the process thus instigated resulted in the doctors providing better quality patient care.", "Clinical trial registries are in widespread use to promote transparency around trials and their results.\n To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.\n An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.\n ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.\n Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.\n Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).\n The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.\n In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.\n National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.", "To investigate the feasibility of improving screening for carriers of haemoglobin disorders in general practice by using a nurse facilitator to work with primary care teams and the relevant haematology laboratories; to identify problems in communication between all those involved in delivering the service, and to implement solutions.\n Two year, practice based randomised controlled trial.\n North London area where 29% of residents and 43% of births are in ethnic groups at risk for haemoglobin disorders. Subjects: 26 of the 93 practices using the services of the area's haematology laboratory agreed to take part and were randomly divided into control and intervention practices.\n Change in number of requests for screening tests for haemoglobin disorders made by control and intervention practices in baseline and intervention years.\n The number of screening tests requested varied from 0-150 in the 93 practices in the baseline year. Study practices tended to have made a moderate number of requests (10-50) during this period. During the intervention year intervention practices made 292 more requests (99% increase) and control practices made 74 fewer requests (23% decrease; P=0.001 for difference in median change). Four practices, three of which were singlehanded, accounted for 75% of the increase. The number of requests from intervention practices, adjusted for baseline requests, was 3.2 times higher than control practices (P<0.0001).\n General practitioners and practice nurses are willing to undertake a new genetic screening service (or expand an existing one) if they are persuaded that it benefits the health of a significant proportion of their practice population. They need appropriate tools (for example, information materials for carriers and groups at risk), and the laboratory must be sensitive to their needs. Preconceptional carrier screening and counselling need to be coupled with antenatal screening.", "To compare a comprehensive behavioral intervention with an education/control condition in the treatment of patients with fibromyalgia (FM), and to explore the role of mediators of clinical improvement in both groups.\n The effects of the behavioral and education/control interventions were evaluated across a 10 week treatment period and at 6 month followup on measures of pain, depression, disability, pain behaviors, and intervening variables. The behavioral intervention focused on the development of diverse pain coping skills, while the education/control condition presented information on a range of health related topic without emphasizing skill acquisition.\n Although improvement across time was found in depression, self-reported pain behaviors, observed pain behaviors, and myalgia scores, no differences in these criteria were found between the behavioral and education/control conditions. Multiple regression analyses revealed that changes in helplessness and passive coping were associated with improvement in a number of clinical outcomes.\n The findings illustrate the value of psychoeducational interventions in decreasing the psychological and behavioral effect of FM, and the value of reducing dysfunctional coping and helplessness in future intervention research.", "To report acceptability, feasibility, and outcome data from a randomized clinical trial (RCT) of a brief intervention for caregivers of children newly diagnosed with cancer.\n Eighty-one families were randomly assigned following collection of baseline data to Intervention or Treatment as Usual (TAU). Recruitment and retention rates and progression through the protocol were tracked. Measures of state anxiety and posttraumatic stress symptoms served as outcomes.\n Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria (40%) and an unexpectedly low participation rate (23%). However, movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback. Outcome data showed no significant differences between the arms of the RCT.\n There are many challenges inherent in conducting a RCT shortly after cancer diagnosis. Consideration of alternative research designs and optimal timing for interventions are essential next steps.", "Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.\n All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.\n Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).\n Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis." ]

[ "320856" ]

[ "Quantitative evaluation of vitamin E in the treatment of angina pectoris." ]

[ "Because of previous reports of the beneficial effect of vitamin E in angina pectoris patients, 48 patients, with both stable angina and positive (chest pain plus ishemic ST depression) maximal exercise treadmill tests, participated in a double-blind cross-over study of 6 months of vitamin E and 6 months of placebo therapy, separated by a 2 month no treatment period. All 48 patients had positive selective coronary arteriograms (75 per cent obstruction of at least a major coronary artery) and/or Q wave ECG evidence of previous myocardial infarction (Minnesota criteria). Evaluation of drug effectiveness was based on performance of serial maximal exercise treadmill tests, serial systolic time interval measurements, and daily angina diaries. No statistically significant differences between the two treatment studied. It is concluded that a large dose of vitamin E (1,600 I.U. of d-alpha-tocopherol succinate daily) for 6 months in patients with stable angina pectoris fails to increase the exercise capacity, improve left ventricular function, or reduce the frequency of chest pain." ]

[ "8229541", "11871742", "1403448", "15629973", "18216861", "9351723", "16843936", "21463215" ]

[ "Gastrointestinal tolerance, fat absorption, plasma ketone and urinary dicarboxylic acid levels in low-birth-weight infants fed different amounts of medium-chain triglycerides in formula.", "Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized, controlled trial comparing nutrient formulas.", "Comparison of two preterm formulas with or without addition of medium-chain triglycerides (MCTs). I: Effects on nitrogen and fat balance and body composition changes.", "Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.", "The early use of minimal enteral nutrition in extremely low birth weight newborns.", "A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.", "Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn's disease.", "The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/septicemia in premature neonates." ]

[ "This study was conducted to evaluate the effect of medium-chain triglycerides (MCT) in a formula for low-birth-weight (LBW) infants on gastrointestinal tolerance, fat absorption, plasma ketone levels, and urinary dicarboxylic acid (DCA) excretion. At the start of enteral feedings, 64 LBW infants (< or = 1500 g) were randomly assigned to one of four experimental formulas. The formulas contained either 0, 17, 34, or 50% of the total fat as MCT oil. The nonfat constituents of all four formulas were the same and identical to Similac Special Care 24 (SCF). Infants were studied from the start of enteral feeding until approximately 7 days after reaching full feeds. Growth and tolerance were assessed in all infants over the entire feeding period. A 48-h balance study was conducted after enteral intake exceeded 100 kcal/kg/day for 3 days. Stool fat, plasma D-(-)-3-hydroxybutyrate (3HB) and carnitine, serum glucose, and urinary DCA levels were determined. Groups did not differ in growth, formula intake, fat absorption (76-84%), serum glucose, or plasma carnitine levels. Gastrointestinal tolerance was excellent and did not differ among groups. Plasma 3HB was significantly different (p < 0.05) only between the 0 and 50% MCT groups, 50 +/- 10 versus 120 +/- 20 microM, respectively. The excretion of urinary DCAs increased with increasing amounts of MCT in the formula. In conclusion, fat absorption and gastrointestinal tolerance were not affected by different MCT levels (0 to 50% of the total fat), but higher levels of plasma 3HB and urinary DCAs were associated with higher levels of MCT in the LBW formulas studied.", "The optimal dietary fat content to induce clinical remission in active Crohn's disease has been the subject of controversy. We therefore performed a prospective, randomized, controlled study to compare the effects of nutrient formulas differing in the amount of medium-chain triglycerides (MCT).\n Thirty-six patients with active Crohn's disease whose Crohn's disease activity index (CDAI) was > or =150 were included in the study. A formula with 3.4 g of fat per 2000-kcal dose was used as the nutrient formula with a low-fat content (ED group), and a formula with 55.6 g of fat per 2000-kcal dose was used as the nutrient formula with a high amount of MCT (TL group).\n The rate of short-term remission induction at 6 weeks was 67% in the ED group and 72% in the TL group (p = NS). Therapy markedly reduced the high CDAI and van Hees activity index in both groups, with no significant difference in the pattern of the time-course changes. C-reactive protein levels, erythrocyte sedimentation rate, and low serum albumin and plasma prealbumin levels normalized over the course of therapy, with no significant difference between the 2 groups. The assessment of fatty acid fractions revealed that the triene/tetraene ratio began to increase at 2 weeks in the ED group. The serum levels of linoleic acid, an omega-6 fatty acid, almost always varied within the normal range during the treatment period in the TL group, but in the ED group, levels began to decrease significantly at 2 weeks. The levels of linolenic acid, an omega-3 fatty acid, decreased in both groups.\n Both nutrient formulas induced clinical remission in about two-thirds of patients. The results of the present study suggest that it is not necessary to restrict the amount of MCT when given in liquid form to patients with active Crohn's disease.", "Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on nitrogen and fat balances and macronutrient oxidation were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There were no differences in nitrogen absorption or in excretion. Median nitrogen retention was 74% (MCT) vs. 71% (LCT) of intake. Fat absorption was higher (p less than 0.05) in the MCT group (88%) vs. 79% in the LCT group (median values). MCTs did not stimulate fat oxidation as measured by indirect calorimetry, so fat deposition was also higher on the MCT formula. As weight gain was not different between groups, the percentage of weight gain consisting of fat accretion was significantly (p less than 0.005) higher with the MCT formula (24% vs. 21%). On the other hand, there was no increase in percent protein accretion (both 15% of weight gain). We conclude that the existence of a slightly lower fat absorption in the healthy growing neonate fed a LCT formula compared with a MCT formula does not impair growth or nitrogen retention, but merely induces a slight decrease in the high relative fat accretion encountered in the preterm neonate.", "We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.\n A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2).\n Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species.\n Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.", "To gather information regarding the efficacy of early minimal enteral nutrition on overall feeding tolerance in extremely low birth weight infants.\n Prospective randomized controlled trial comparing the early use of minimal enteral nutrition in extremely low birth weight infants from day 2 to day 7 vs control infants. On day 8, feeding volume in both groups were advanced by 10 ml kg(-1) day(-1) until full enteral feedings were reached. Time to full feeds, number of intolerance episodes, anthropometric measurements, peak total bilirubin levels, incidence of necrotizing enterocolitis and incidence of sepsis were compared between the two groups with t-test and chi (2) test.\n Eighty-four infants were enrolled in the study but only 61 infants completed the feeding protocol. No statistically significant differences were found between the groups with regards to growth patterns, feeding tolerance, mortality, length of hospital stay and incidence of sepsis and necrotizing enterocolitis.\n Early minimal enteral nutrition use in extremely low birth weight infants did not improve feeding tolerance.", "The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.\n Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.\n Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.\n Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.\n Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.", "Elemental diets are effective treatments for active Crohn's disease. To determine which dietary constituents are of therapeutic importance, the effectiveness of four separate feeds was related to their compositions, and the findings substantiated by meta-analysis of previous dietary studies. 76 patients with active Crohn's disease were recruited. 17 were randomised to an amino acid-based elemental diet (E028), 22 to E028 with added long-chain triglyceride (E028 LCT), 18 to a semi-elemental, peptide based diet (Pepdite 2+) and 19 received E028 with added medium-chain triglyceride (E028 MCT). Disease activity fell in all groups and remission rate was negatively correlated with the amount of energy derived from LCT (r = -0.97, p = 0.016). Inflammatory indices fell in the groups (E028 + E028 MCT) containing least LCT. No other dietary constituents correlated with remission rate. A meta-analysis of published studies confirmed a negative correlation between remission rate and LCT (r = -0.63, p = 0.006) but not other constituents. The association between dietary LCT and remission rate may have pathogenic significance and allow the development of more effective enteral feeds.", "To examine the impact of oral glutamine (Gln) supplementation on gut integrity and on the incidence of necrotizing enterocolitis (NEC)/septicemia of premature neonates.\n Preterm neonates (n = 101, gestational age <34 weeks, birth weight <2000 g) were randomly allocated to receive from day 3 to day 30 postpartum, either oral Gln (0.3 g/kg/day, n = 51-Gln group) or placebo (caloreen-isocaloric, n = 50-control group). Intestinal permeability was determined from the urinary lactulose/mannitol recovery (L/M ratio) following their oral administration and assessed at three time points: day 2 (before first administration), day 7 and day 30 of life. The incidence of NEC and septicemia over the study period was also recorded.\n A decrease of lactulose recovery at days 7 (p = 0.001) and 30 (p < 0.001) and a decrease of L/M ratio at day 7 (p = 0.002) were observed only in the Gln group. Lactulose recovery and L/M ratio at day 7 (p = 0.022 and p = 0.004, respectively), as well as lactulose recovery (p = 0.001), mannitol recovery (p = 0.042), and L/M ratio (p = 0.001) at day 30, were decreased in the Gln group as compared to controls. NEC and septicemia were lower in the Gln group at the end of the first week (p = 0.009 and p = 0.041, respectively) and up to the end of the study (p < 0.001 and p = 0.048, respectively).\n Oral Gln administration may have beneficial effects on intestinal integrity and the overall incidence of NEC/septicemia in preterm infants." ]

[ "22624531", "22738085", "16790652", "18542921", "21857015", "9503219", "11331169", "6190466", "17054812", "19019650", "21775917", "20214205", "7661335", "19050085", "20591890", "9527402", "21366943", "10890478", "20179007", "22248750", "2427448", "12665995", "9361342", "18492315", "10553822", "15127186", "18184958", "8672323", "14575293", "10548199", "15712076", "8694302" ]

[ "Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study.", "Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.", "The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery.", "A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock.", "Resuscitation with hydroxyethyl starch improves renal function and lactate clearance in penetrating trauma in a randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe Trauma).", "Volume therapy in the critically ill: is there a difference?", "Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment.", "Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock.", "A total balanced volume replacement strategy using a new balanced hydoxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery.", "Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients.", "Hydroxyethyl starch resuscitation reduces the risk of intra-abdominal hypertension in severe acute pancreatitis.", "Therapeutic influence of 20 % albumin versus 6% hydroxyethylstarch on extravascular lung water in septic patients: a randomized controlled trial.", "[Comparison of postoperative volume therapy in heart surgery patients].", "Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial.", "A prospective randomized study to evaluate the renal impact of surgical revascularization strategy in diabetic patients.", "A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis.", "[The study of hypertonic saline and hydroxyethyl starch treating severe sepsis].", "Volume therapy with a new hydroxyethyl starch solution in cardiac surgical patients before cardiopulmonary bypass.", "N-acetylcysteine does not prevent hepatorenal ischaemia-reperfusion injury in patients undergoing orthotopic liver transplantation.", "[The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock].", "[Volume replacement with a new hydroxyethyl starch preparation (3 percent HES 200/0.5) in heart surgery].", "Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin.", "Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.", "Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial.", "The influence of different intravascular volume replacement regimens on renal function in the elderly.", "Fluid resuscitation with colloids of different molecular weight in septic shock.", "Intensive insulin therapy and pentastarch resuscitation in severe sepsis.", "Does the type of volume therapy influence endothelial-related coagulation in the critically ill?", "Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)--what is the procedure of choice in critically ill patients?", "Comparison of the acute hemodynamic effects of hypertonic or colloid infusions immediately after mitral valve repair.", "Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit.", "The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients." ]

[ "ABSTRACT: INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALS.GOV: NCT00464204.", "Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.\n In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.\n Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.\n Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).", "The value of human albumin (HA) for treating hypovolemia is controversial. Less expensive alternatives such as hydroxyethyl starch (HES) are sometimes refused because of unwanted side effects. We prospectively randomized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5% HA (n = 25) or a third generation HES preparation (6% HES 130/0.4; n = 25) when mean arterial blood pressure was <60 mm Hg and central venous pressure was <10 mm Hg. Hemodynamics, inflammation (interleukin-6), endothelial activation-integrity (adhesion molecules), coagulation (thrombelastography), and renal function (including kidney-specific proteins) were monitored after the induction of anesthesia, after surgery, 5 h in the intensive care unit, and on the first postoperative day. HA patients received 3960 +/- 590 mL of HA and 5070 +/- 1030 mL of Ringer's lactate solution, and HES patients received 3500 +/- 530 mL of HES and 4550 +/- 880 mL of Ringer's lactate solution. Total protein remained normal only in the HA-treated patients. No significant differences (P > 0.1) between the groups were seen with regard to hemodynamics, coagulation, and kidney function. Plasma levels of interleukin-6 and soluble adhesion molecules were significantly (P < 0.05) higher in the HA- than in the HES-treated patients. We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation. Because of the decreased inflammatory response and endothelial activation-injury, HES 130/0.4 seems to be the more appropriate fluid strategy for these patients.", "High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF).\n Prospective randomized study in an intensive care unit (ICU).\n Twenty patients with septic shock and ARF.\n Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg.\n We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected.\n HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival.", "The role of fluids in trauma resuscitation is controversial. We compared resuscitation with 0.9% saline vs hydroxyethyl starch, HES 130/0.4, in severe trauma with respect to resuscitation, fluid volume, gastrointestinal recovery, renal function, and blood product requirements.\n Randomized, controlled, double-blind study of severely injured patients requiring >3 litres of fluid resuscitation. Blunt and penetrating trauma were randomized separately. Patients were followed up for 30 days.\n A total of 115 patients were randomized; of which, 109 were studied. For patients with penetrating trauma (n=67), the mean (sd) fluid requirements were 5.1 (2.7) litres in the HES group and 7.4 (4.3) litres in the saline group (P<0.001). In blunt trauma (n=42), there was no difference in study fluid requirements, but the HES group required significantly more blood products [packed red blood cell volumes 2943 (1628) vs 1473 (1071) ml, P=0.005] and was more severely injured than the saline group (median injury severity score 29.5 vs 18; P=0.01). Haemodynamic data were similar, but, in the penetrating group, plasma lactate concentrations were lower over the first 4 h (P=0.029) and on day 1 with HES than with saline [2.1 (1.4) vs 3.2 (2.2) mmol litre⁻¹; P=0.017]. There was no difference between any groups in time to recovery of bowel function or mortality. In penetrating trauma, renal injury occurred more frequently in the saline group than the HES group (16% vs 0%; P=0.018). In penetrating trauma, maximum sequential organ function scores were lower with HES than with saline (median 2.4 vs 4.5, P=0.012). No differences were seen in safety measures in the blunt trauma patients.\n In penetrating trauma, HES provided significantly better lactate clearance and less renal injury than saline. No firm conclusions could be drawn for blunt trauma. Study registration: ISRCTN 42061860.", "There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA).\n Prospective, randomized study.\n Clinical investigations on a surgical intensive care unit (ICU) of a university hospital.\n 150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed.\n Either 10% low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20% HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen.\n In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively (\"baseline\" value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 +/- 0.5 to 1.5 +/- 0.4 mg/dl). Volume replacement using albumin was significantly (p < 0.001) more costly than therapy with HES.\n Volume therapy with 10% HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20% albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin--even for prolonged volume therapy in the critically ill patient.", "To examine the effects of hydroxyethyl starch (HES) on renal function.\n Randomized, controlled trial.\n Operating theatre of a university hospital.\n 60 ASA physical status I and II male patients undergoing middle ear surgery.\n Patients received either lactated Ringer's solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.\n Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously.\n There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups.\n Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation.", "A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings.", "The kind of fluid for correcting hypovolaemia is still a focus of debate. In a prospective, randomized, controlled and double-blind study in patients undergoing major abdominal surgery, a total balanced volume replacement strategy including a new balanced hydroxyethyl starch (HES) solution was compared with a conventional, non-balanced fluid regimen.\n In Group A (n = 15), a new balanced 6% HES 130/0.42 was given along with a balanced crystalloid solution; in Group B (n = 15), an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid (saline solution) were administered. Volume was given when mean arterial pressure (MAP) was <65 mmHg and central venous pressure (CVP) minus positive end-expiratoric pressure (PEEP) level was <10 mmHg. Haemodynamics, acid-base status, coagulation (thrombelastography (TEG)) and kidney function (including kidney-specific proteins, N-acetyl-beta-d-glucosaminidase (beta-NAG) and alpha-1-microglobulin) were measured after induction of anaesthesia, at the end of surgery, 5 and 24 h after surgery.\n Group A received 3533 +/- 1302 mL of HES and 5333 +/- 1063 mL of crystalloids, in Group B, 3866 +/- 1674 mL of HES and 5966 +/- 1202 mL of crystalloids were given. Haemodynamics, laboratory data, TEG data and kidney function were without significant differences between the groups. Cl- concentration and base excess (-5 +/- 2.4 mmol L-1 vs. 0.4 +/- 2.4 mmol L-1) were significantly higher in patients of Group B than of Group A.\n A complete balanced volume replacement strategy including a new balanced HES preparation resulted in significantly less derangement in acid-base status compared with a non-balanced volume replacement regimen. The new HES preparation showed no negative effects on coagulation and kidney function.", "To compare the hemodynamic effects of two different concentrations of pentastarch hydroxyethyl starch (HES; 200/0.5) solutions with a 4% human albumin solution for fluid resuscitation.\n Open-label, randomized, controlled study.\n Medical-surgical intensive care unit.\n 34 consecutive, hemodynamically stable, adult patients with sepsis and suspected hypovolemia.\n Patients received a 400 mL infusion of either 10% HES (n = 11), 6% HES (n = 10), or 4% albumin (n = 13) over 40 minutes.\n Hemodynamic and blood data were collected 40, 70, 100, and 160 minutes after the start of the fluid challenge.\n Cardiac index, stroke volume index, and left ventricular stroke work index increased more in the 10% HES group than the 6% HES or albumin groups (P < 0.05). Oxygen delivery increased only in the 10% HES group. A decrease in hemoglobin concentration occurred in all three groups but was greatest in the 10% HES group.\n HES is as effective as albumin for volume resuscitation in septic patients.", "This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages.\n Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8.\n The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days).\n Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.", "Recent studies demonstrated that extravascular lung water (EVLW) is a reliable and independent marker for outcome. The primary therapeutically goal in critically ill patients is to resuscitate and retain adequate organ perfusion by fluid administration, where is necessary to achieve adequate intravascular filling, but avoid initiation of pulmonary edema.\n Patients with severe sepsis were randomly allocated to a group treated with 20% Albumin 100 ml every 12 hours (ALB; n = 30) or with 6% hydroxyethylstarch 130/0, 4 250 ml every 6 hours (HES; n = 26). Both treatments were completed by crystalloids or norephinephrin as necessary. We analyzed amount of developed EVLW, and relation with mortality, PaO2/FiO2 and alveolo-arterial oxygen difference.\n We observed significantly greater decrease of EVLW when compared with baseline during whole monitored period of 72 hours in ALB group in contrast to HES patients (p < 0.05). Despite no significant changes of EVLW in HES group, we noted improve of PaO2/FiO2 and AaDO2 in both groups. We did not observed significant difference in mortality.\n The present study results show can summarize that albumin reduces in a higher amount and earlier the extravascular lung water than HES, but this reduction was not associated with improvement of oxygenation functions, which was better in HES group.", "Patients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline).\n Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany).\n Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens.\n We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h.", "It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.\n At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.\n Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.\n The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock.", "Acute kidney injury (AKI) is a major postoperative complication following cardiac surgery. Diabetes mellitus is a major cause of nephropathy and end-stage renal failure. We aimed to evaluate the occurrence of adverse renal outcomes, in diabetic patients, between on-pump (CPB) and off-pump (OPCAB) coronary artery bypass graft (CABG). Seventy-one diabetic patients (36 and 35 patients in the CPB and OPCAB groups, respectively) were enrolled in a prospective randomized study. Renal tubular and glomerular functions, were monitored preoperatively and over five consecutive days. There was no significant difference between the groups in terms of age, gender, New York Heart Association class, Canadian Cardiovascular Society functional classification of angina grade and number of CABG. Intensive care unit stay, duration of intubation, hospital stay and bleeding were significantly higher in the CPB group. No significant differences in plasmatic creatinine, urinary creatinine, creatinine clearance, proteinuria or osmolality were detected. A significant rise in urinary albumine excretion occurred in both groups peaking on the operative day; for the on-pump CABG group (10±5 vs. 48±57; P=0.015) and for the OPCAB group (11±6 vs. 37±59; P=0.04). Values were less important in the OPCAB group and return to the baseline was faster than in the CPB group. OPCAB attenuates sub-clinical AKI, in diabetic patients.", "The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.", "To evaluate the effect of 7.5% hypertonic saline (HS) and 6% hydroxyethyl starch (HES) 130/0.4 on early fluid resuscitation for severe sepsis.\n Prospective randomized control trial was carried out in intensive care unit (ICU) of the Affiliated Hospital of Jianghan University. One hundred and thirty five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7.5% HS and 6% HES 130/0.4 500 ml, those in HES group received lactated Ringer solution following 6% HES 130/0.4 500 ml, and those in the lactated Ringer group (RL group) received lactated Ringer solution only.Mean arterial pressure (MAP), oxygenation index (PaO₂/FiO₂),arterial lactate (Lac),lactate clearance rate, acute physiology and chronic health evaluation II(APACHEII) score,fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome (MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission.\n At 6 hours after ICU admission,MAP[mm Hg (1 mm Hg=0.133 kPa): 68.7 ± 3.0], PaO₂/FiO₂(mm Hg: 262.2 ± 17.4), lactate clearance rate [(21 ± 4)%] in HS+HES group were significantly higher than those in HES group [MAP: 63.8 ± 3.5,PaO(2)/FiO(2): 252.0 ± 21.2, lactate clearance rate: (11 ± 2)%] and RL group [MAP: 62.6 ± 3.6, PaO₂/FiO₂:248.4 ± 17.0,lactate clearance rate: (9 ± 1)%, all P <0.01]. Arterial Lac in HS+HES group (mmol/L: 3.5 ± 0.7) was significantly lower than that in HES group (4.1 ± 0.7) and RL group (4.0 ± 0.7, both P <0.01). There was no significant difference in APACHE II score between HS+HES group (13.2 ± 1.9) and HES group (14.0 ± 1.6), and the APACHEII score in HS+HES group was significantly lower than that in RL group (15.2 ± 1.7, P <0.01). At 24 hours after ICU admission, PaO₂/FiO₂ (mm Hg: 303.3 ± 17.3) was significantly higher in HS+HES group than that in HES group (282.9 ± 21.1) and RL group (268.9 ± 15.2, both P <0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHEII score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group (ml, 6 hours: 1 877.8 ± 215.2, 24 hours: 5 475.6 ± 208.8) was markedly less than that in HES group (6 hours: 2 505.6 ± 276.2, 24 hours: 6 383.3 ± 287.4) and RL group (6 hours: 3 496.7 ± 325.5,24 hours: 7 439.6 ± 229.6), yet urine output in HS+HES group (ml, 6 hours: 294.2 ± 36.9, 24 hours : 2 793.8 ± 37.1) was significantly higher than that in HES group (6 hours: 248.9 ± 25.3, 24 hours : 2 248.9 ± 25.3) and RL group (6 hours: 178.9 ± 14.8, 24 hours: 2 000.4 ± 147.0, all P <0.01). The incidence of MODS in HS+HES group (6.7%) was statistically lower than that in RL group (28.9%, P <0.05), while no obvious difference was found between HS+HES group and HES group (17.8%, P >0.05). There was no significant difference in mortality among three groups (HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P >0.05).\n 7.5%HS and 6%HES 130/0.4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS.", "To compare the hemodynamic efficacy of a new hydroxyethyl starch (HES) preparation (130/0.4) with an HES 200/0.5 solution.\n Prospective, randomized, double-blind, phase II study.\n An urban, university-affiliated hospital.\n Twenty patients undergoing elective first-time cardiac surgery.\n After induction of anesthesia and before the start of surgery, a new HES 130/0.4 (molecular weight, 130,000 d; degree of substitution, 0.4) (n = 10) or HES 200/0.5 (molecular weight, 200,000 d; degree of substitution, 0.5) (n = 10) was infused (10 mL/kg) within 30 minutes when pulmonary capillary wedge pressure was less than 10 mmHg.\n Extensive hemodynamic monitoring was performed 30 and 60 minutes after the end of infusion. Then surgery was started. Standard laboratory parameters were measured before surgery and on the 1st postoperative day. A similar amount of HES was given in both groups (HES 130, 795+/-75 mL; HES 200, 820+/-90 mL). Filling pressures (central venous pressure, pulmonary capillary wedge pressure) and cardiac index increased similarly in both groups and remained significantly elevated 60 minutes after the end of infusion. All other hemodynamic parameters were similar between the two volume groups. Renal (creatinine) and hepatic function (aspartate aminotransferase, alanine aminotransferase) and hemostasis (platelet count, activated partial thromboplastin time, blood loss) were without group differences until the morning of the 1st postoperative day.\n The new 6% HES 130/0.4 was as effective as a 6% HES 200/0.5 preparation in regard to hemodynamic efficacy. No negative side effects on organ function were seen. The 6% HES 130/0.4 solution may become an alternative strategy for volume therapy in cardiac surgery.", "Glutathione (GSH) acts as a free radical scavenger that may be helpful in preventing reperfusion injury. N-acetylcysteine (NAC) replenishes GSH stores. The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury (AKI).\n Our study was a randomized, double-blind, placebo-controlled trial of 100 patients; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous (IV) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses. Both groups were followed up for 1 year post-orthotopic liver transplant (OLT). We recorded liver function tests, renal function tests, graft survival, patient survival, plasma GSH and duration of hospital and ICU stay. In addition to serum creatinine (SCr) levels, we analysed cystatin C and beta-trace as independent measures of glomerular filtration. All clinical data were recorded daily for the first week after the surgery, then on Days 14, 21, 30, 90 and 180 and at the end of the first year.\n IV NAC did not affect survival, graft function or risk of AKI. However, GSH levels were highly variable with only 50% of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased. Additional risk factors for AKI in the post-transplant period were female gender (P = 0.05), increased baseline serum bilirubin (P = 0.004) and increased baseline SCr levels (P = 0.02).\n IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation. The dose and duration of NAC used, though higher than most renal protection studies, may have been ineffective for raising GSH levels in some patients.", "To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock.\n Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded.\n ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05).\n Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.", "In a randomized study including 55 patients undergoing elective aorto-coronary bypass surgery efficacy of a low concentrated hydroxyethylstarch (3% HES 200/0.5) was tested after extracorporeal circulation (ECC). All patients received 1,000 ml autologous washed erythrocytes (cell saver) and 400 ml fresh frozen plasma (FFP). Thereafter patients were randomized into 4 groups. Hemodynamic parameters, laboratory parameters as well as extravascular lung water (EVLW - double indicator dilution technique) were measured before ECC as well as before and after infusion therapy. With regard to hemodynamic efficiency and the change in laboratory data no relevant differences between group I, II and III could be seen. EVLW-measurement demonstrated the lowest increase in lung water after infusion of HES; simultaneously pulmonary gas exchange was less compromised in comparison to the other infusion groups. 3% HES 200/0.5 solution can be considered as an effective volume substitute with short intravascular retention time, which seems to be of advantage in patients coming off extracorporeal circulation.", "There is continuing concern on the influence of hydroxethyl starch (HES) on renal function.\n Prospective, randomized study.\n University-affiliated medical center.\n Forty consecutive patients aged >70 years undergoing cardiac surgery using cardiopulmonary bypass.\n Either low-molecular HES (mean molecular weight: 130 kD) with low degree of substitution (0.4) (6% HES 130/0.4) (n=20) or gelatin ( n=20) was given after induction of anesthesia until the 2nd postoperative day (POD) to keep central venous pressure between 12-14 mmHg.\n Creatinine clearance (CC) and fractional sodium clearance (FSC) were measured. N-acetyl-beta-D-glucosamidase, alpha-1-microglobulin, glutathione transferase-pi, and glutathione transferase-alpha were measured from urine specimens. Measurements were made after induction of anesthesia, at the end of surgery, and at the first and the second POD. More gelatin (total: 4150+/-490 ml) than HES 130/0.4 (total: 3450+/-450 ml) was infused within the study. CC and FSC were without differences between the two groups. All measured kidney-specific proteins were almost within normal range at baseline. They increased significantly after surgery, however, without significant group differences. At the 2nd POD, kidney-specific proteins had returned almost to normal values. None of the patients developed acute renal failure.\n Sensitive markers of kidney dysfunction increased in our elderly patients indicating moderate alterations in kidney integrity during cardiac surgery. The two volume replacement regimens did not differ with regard to kidney integrity in elderly patients undergoing cardiac surgery.", "Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis.", "Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery. This study investigated the safety profile of a recent medium-molecular-weight hydroxyethyl starch (HES) preparation with a low molar substitution (HES 130/0.4) in this sensitive patient group.\n Sixty-five patients were randomly allocated to receive either 6% hydroxyethyl starch (Voluven); n = 32) or 3% gelatin (Plasmion); n = 33) for perioperative volume substitution. At baseline, renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min(-1). The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery.\n Both treatment groups were compared for non-inferiority (pre-defined non-inferiority range hydroxyethyl starch < gelatin + 17.68 micromol L(-1) or 0.2 mg dL(-1). Other renal safety parameters included minimum postoperative creatinine clearance, incidence of oliguria and adverse events of the renal system. Baseline characteristics, surgical procedures and the mean total infusion volume were comparable. Non-inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non-parametric one-sided 95% CI for the difference hydroxyethyl starch-gelatin [-infinity, 11 micromol L(-1)]. Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group. One patient receiving gelatin required dialysis secondary to surgical complications. Two patients of each treatment group died.\n As we found no drug-related adverse effects of hydroxyethyl starch on renal function, we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery.", "Elderly patients are at risk of developing renal dysfunction. Synthetic colloids are often used perioperatively, but they may have detrimental effects on renal function. In a prospective, randomized study, we assessed the influence of different intravascular volume replacement regimens on renal function in elderly (>65 yr) and younger (< 65 yr) patients without preoperative renal dysfunction who were undergoing major abdominal surgery. Either 6% low molecular weight hydroxyethyl starch (HES) solution (mean molecular weight 70,000 D, degree of substitution 0.5; HES 70/0.5) [each group n = 10]), 6% medium-molecular weight HES (molecular weight 200,000 D, degree of substitution 0.5 (HES 200/0.5) [each group n = 10]), or modified gelatin (molecular weight 35,000 D [each group n = 10]) was administered to maintain mean arterial blood pressure >65 mm Hg and central venous pressure between 10 and 14 mm Hg. After the induction of anesthesia (T0); at the end of surgery (T1); 4 h after surgery (T2); and on the first (T3), second (T4), and third postoperative days (T5), alpha1-microglobulin (alpha1-M), N-acetyl-beta-glucosaminidase, fractional sodium clearance, and creatinine clearance (CC) were measured. Colloids (1300-3000 mL) were infused until the first postoperative day. At T0, urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups (P < 0.05). alpha1-M remained increased only in the gelatin group. N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups. At baseline, CC was significantly higher in the younger than in the elderly patients, but CC did not decrease in any of the intravascular volume replacement groups. We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction.\n We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery. Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics. As assessed by sensitive markers of renal function, all three regimens can be used safely for volume replacement without risking significant renal dysfunction.", "The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI).\n Prospective randomised clinical trial.\n Twenty-bed intensive care unit in a university hospital.\n Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI <850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each).\n For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI >900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used.\n ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg).\n The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation.", "The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.\n In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.\n The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.\n The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)\n 2008 Massachusetts Medical Society", "The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation.", "Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so.", "To determine the acute hemodynamic effect of hypertonic saline and/or colloid solutions as volume resuscitation in postoperative mitral valve repair patients.\n Prospective, randomized trial.\n Postoperative cardiac intensive care unit of Broussais Hospital.\n Twenty-six patients who underwent mitral valve repair were prospectively studied. Two patients were excluded during the study.\n During the immediate postoperative period, when wedge pressure decreases to <8 mm Hg, patients were randomly assigned to receive 250 mL of either hypertonic saline 7.2%-hydroxyethyl starch 6% (molecular weight, 200,000; hydroxyethylation ratio, 0.5) solution (HS-HES group), hypertonic saline 7.2% solution (HS group), or hydroxyethyl starch 6% solution (HES group). The infusion was completed within 15 mins. No additional volume was infused throughout the study.\n Standard hemodynamic measurements and echocardiographic data demonstrated that HS-HES and HS induced a higher increase in left ventricular end-diastolic area than HES. In the HS-HES and HS groups, systemic vascular resistances decreased significantly and end-systolic area tended to decrease. In the HES group, systemic vascular resistances did not change and end-systolic area tended to increase. Accordingly, ejection fraction increased significantly by 21% and 18% with HS-HES (from 50.5 +/- 5.5 to 61.2 +/- 4.8) and HS (from 49.7 +/- 3.6 to 58.8 +/- 3.3), respectively, and did not change with HES. A major increase in cardiac index was observed after hypertonic solutions infusion, from 2.9 +/- 0.3 to 4.1 +/- 0.4 L/min/m2 in the HS-HES group and from 2.7 +/- 0.3 to 3.8 +/- 0.4 L/min/m2 in the HS group. Then, cardiac index progressively returned to baseline values within the 3 hrs after the infusion. No significant difference was observed between HS-HES and HS. In these groups, plasma sodium increased significantly after the infusion and remained higher than baseline values throughout the study. Adverse events were observed only with hypertonic solution administration: hypotensive episodes, sudden increases in pulmonary capillary wedge pressure, and ventricular arrhythmias. These side effects are likely attributable to a too-high dose and/or rate of infusion. All patients included in the study were discharged from the hospital before the 10th postoperative day.\n We conclude that in patients who have undergone mitral valve repair, postoperative infusion of hypertonic saline solutions increases left ventricular preload and left ventricular ejection fraction. The use of these hypertonic solutions may be of interest in patients with valvular cardiomyopathy. A titrated dose and a low rate of infusion may substantially improve the safety.", "Metabolic acidosis is the best predictor of death in children with severe falciparum malaria; however, its treatment presents a therapeutic dilemma, because acidosis and hypovolemia may coexist with coma, which can be associated with elevated intracranial pressure. We postulated that volume resuscitation with albumin might correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid. In an open-label, randomized, controlled trial, we compared the safety of resuscitation with albumin to saline in Kenyan children with severe malaria.\n We randomly assigned children with severe malaria and metabolic acidosis (base deficit, >8 mmol/L) to receive fluid resuscitation with either 4.5% albumin or normal saline. A control (maintenance only) group was only included for patients with a base deficit of <15 mmol/L. The primary outcome measure was the percentage reduction in base deficit at 8 h. Secondary end points included death, the requirement for rescue therapies, and neurological sequelae in survivors.\n Of 150 children recruited for the trial, 61 received saline, 56 received albumin, and 33 served as control subjects. There was no significant difference in the resolution of acidosis between the groups; however, the mortality rate was significantly lower among patients who received albumin (3.6% [2 of 56 patients]) than among those who received saline (18% [11 of 61]; relative risk, 5.5; 95% confidence interval, 1.2-24.8; P=.013).\n In high-risk children with severe malaria and acidosis, fluid resuscitation with albumin may reduce mortality. Our study design did not enable us to determine whether saline administration is preferable to fluid restriction or whether saline administration is actually hazardous. Further studies are needed to confirm our findings before definitive treatment recommendations can be made.", "Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy." ]

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[ "Effect of a physical therapeutic intervention for balance problems in the elderly: a single-blind, randomized, controlled multicentre trial.", "A comparison of the effects of three types of endurance training on balance and other fall risk factors in older adults.", "Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial.", "Effect of music-based multitask training on gait, balance, and fall risk in elderly people: a randomized controlled trial.", "A randomized controlled trial of an enhanced balance training program to improve mobility and reduce falls in elderly patients.", "A clinical trial of strengthening and aerobic exercise to improve gait and balance in elderly male nursing home residents.", "The effects of multidimensional home-based exercise on functional performance in elderly people.", "A community-based fitness and mobility exercise program for older adults with chronic stroke: a randomized, controlled trial.", "Sensory-specific balance training in older adults: effect on proprioceptive reintegration and cognitive demands.", "The efficacy of a specific balance-strategy training programme for preventing falls among older people: a pilot randomised controlled trial.", "Multifactorial intervention with balance training as a core component among fall-prone older adults.", "Use of visual feedback in retraining balance following acute stroke.", "LiFE Pilot Study: A randomised trial of balance and strength training embedded in daily life activity to reduce falls in older adults.", "New intervention program for preventing falls among frail elderly people: the effects of perturbed walking exercise using a bilateral separated treadmill.", "Comparison of the effectiveness of two programmes on older adults at risk of falling: unsupervised home exercise and supervised group exercise.", "Can elderly patients who have had a hip fracture perform moderate- to high-intensity exercise at home?", "A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke.", "Exercise and functional tasks among adults who are functionally limited.", "The effect of strength and endurance training on gait, balance, fall risk, and health services use in community-living older adults.", "Effectiveness of aquatic and non-aquatic lower limb muscle endurance training in the static and dynamic balance of elderly people.", "A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia.", "A multi-component exercise regimen to prevent functional decline and bone fragility in home-dwelling elderly women: randomized, controlled trial.", "Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke.", "A randomized controlled trial of weight-bearing versus non-weight-bearing exercise for improving physical ability after usual care for hip fracture.", "Effects of resistive and balance exercises on isokinetic strength in older persons.", "Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial.", "Dual-task exercise improves walking ability in chronic stroke: a randomized controlled trial.", "Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques.", "The effect of a task-oriented walking intervention on improving balance self-efficacy poststroke: a randomized, controlled trial.", "Effects of a group exercise program on strength, mobility, and falls among fall-prone elderly men.", "The effect of a 12-week dynamic resistance strength training program on gait velocity and balance of older adults.", "Community-based exercise program reduces risk factors for falls in 65- to 75-year-old women with osteoporosis: randomized controlled trial.", "Changes in postural balance in frail elderly women during a 4-week visual feedback training: a randomized controlled trial.", "Fall incidence in frail older women after individualized visual feedback-based balance training.", "Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.", "Effects of a physical and nutritional intervention program for frail elderly people over age 75. A randomized controlled pilot treatment trial.", "Whole body vibration versus conventional physiotherapy to improve balance and gait in Parkinson's disease.", "Low-intensity exercise and reduction of the risk for falls among at-risk elders.", "Moderate exercise improves gait stability in disabled elders.", "Otago home-based strength and balance retraining improves executive functioning in older fallers: a randomized controlled trial.", "Reducing risk of falling in older people discharged from hospital: a randomized controlled trial comparing seated exercises, weight-bearing exercises, and social visits.", "Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial.", "Self-paced resistance training and walking exercise in community-dwelling older adults: effects on neuromotor performance.", "Effects of brisk walking on static and dynamic balance, locomotion, body composition, and aerobic capacity in ageing healthy active men.", "Functional vs. strength training in disabled elderly outpatients.", "A randomised trial of weight-bearing versus non-weight-bearing exercise for improving physical ability in inpatients after hip fracture.", "The feasibility of Whole Body Vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013].", "Randomized controlled trial of exercise intervention for the prevention of falls in community-dwelling elderly Japanese women.", "Preventative effect of exercise against falls in the elderly: a randomized controlled trial.", "Physician-based physical activity counseling for middle-aged and older adults: a randomized trial.", "A randomized trial of a multifaceted intervention to reduce falls among community-dwelling adults.", "Efficacy and effectiveness of a balance-enhancing insole.", "Group exercise can improve participants' mobility in an outpatient rehabilitation setting: a randomized controlled trial.", "Effects of exercise on bone density, balance, and self-efficacy in older women.", "A randomized outcome evaluation of group exercise programs in long-term care institutions.", "A task-orientated intervention enhances walking distance and speed in the first year post stroke: a randomized controlled trial.", "Home-based video exercise intervention for community-dwelling frail older women: a randomized controlled trial.", "The effect of a 12-month exercise trial on balance, strength, and falls in older women: a randomized controlled trial.", "Randomized controlled trial of exercise training for older people (Sendai Silver Center Trial; SSCT): study design and primary outcome.", "A randomized, controlled trial of fall prevention programs and quality of life in older fallers.", "The effect of group exercise on physical functioning and falls in frail older people living in retirement villages: a randomized, controlled trial.", "Getting Grounded Gracefully: effectiveness and acceptability of Feldenkrais in improving balance.", "High-intensity functional exercise program and protein-enriched energy supplement for older persons dependent in activities of daily living: a randomised controlled trial.", "Intensive physical training in geriatric patients after severe falls and hip surgery.", "A five-week exercise program can reduce falls and improve obstacle avoidance in the elderly.", "Effect of exercise on mobility, balance, and health-related quality of life in osteoporotic women with a history of vertebral fracture: a randomized, controlled trial.", "Effect of additional functional exercises on balance in elderly people.", "A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.", "Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures.", "A 1-year combined weight-bearing training program is beneficial for bone mineral density and neuromuscular function in older women.", "Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study.", "Balance improvement in patients with benign paroxysmal positional vertigo.", "Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial.", "A randomized controlled trial of Turkish folklore dance on the physical performance, balance, depression and quality of life in older women.", "Controlled whole body vibration to decrease fall risk and improve health-related quality of life of nursing home residents.", "Response of sagittal plane gait kinematics to weight-supported treadmill training and functional neuromuscular stimulation following stroke." ]

[ "To establish the effect of a short, individualized exercise programme on balance dysfunction in the elderly.\n A single-blind, randomized, controlled, multicentre trial.\n Physical and recreational therapy departments from two rehabilitation centres.\n Ninety-four subjects of >75 years with functional balance problems living independently or in a residential care facility. Seventy-seven subjects completed the intervention period and four-week follow-up. At a one-year follow-up 49 subjects were evaluated on balance functioning.\n Twelve sessions of an individualized balance training programme (experimental group) or 12 sessions of an individualized extra attention programme (control group) given in 4-6 weeks.\n Berg Balance Scale and the Dynamic Gait Index to establish balance functioning, a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression.\n Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group (p f 0.001, p f 0.001, respectively). However the effect disappeared at a one-year follow-up on the Berg Balance Scale. No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme. Results on the other response variables revealed no effect of the intervention.\n A short individualized exercise programme can improve functional balance in people aged 75 years and older. This improvement was maintained at least for one month but had worn off by one year.", "We hypothesized that short-term endurance training improves balance in older adults, if training involves movements that \"stress\" balance. We tested the hypothesis by looking for a dose-response relationship between movement during exercise and balance improvement. The study was a single-blinded, randomized controlled trial. Subjects were sedentary adults (N = 106) aged 68-85 with at least mild deficits in balance. Exercise groups were: stationary cycle (low movement), walking (medium movement), and aerobic movement (high movement). Subjects attended supervised exercise classes three times a week for three months, followed by self-directed exercise of any type for three months. The primary test of the hypothesis compared changes in balance after three months of supervised exercise. One balance measure (distance walked on a six-meter narrow balance beam) improved in the hypothesized dose-response manner (cycle, 3% improvement; walking, 7% improvement; aerobic movement, 18% improvement: p < 0.02, test of trend). Other balance measures did not improve with exercise. Only walking exercise improved gait speed (by 5%, p < 0.02) and SF-36 role-physical score (by 24%, p < 0.05). VO2max improved with walking (18%, p < 0.004) and aerobic movement (10%, p < 0.01), but improved less with cycling (8%, p > 0.1). Leg strength improved significantly in all exercise groups. The study hypothesis was supported only for one balance measure. Only walking improved at least one measure of all major outcomes (endurance, strength, gait, balance, and health status), suggesting that walking is most useful for all prevention. Cycle exercise appeared least useful.", "recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people. However, research is required to determine whether supervised group exercise programmes, conducted in community settings with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group.\n to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance, muscle strength, reaction time, physical functioning, health status and prevents falls in at-risk community-dwelling older people.\n the sample comprised 163 people aged over 65 years identified as at risk of falling using a standardised assessment screen by their general practitioner or hospital-based physiotherapist, residing in South Western Sydney, Australia. Subjects were randomised into either an exercise intervention group or a control group. Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial. Falls were measured over a 12-month follow-up period using monthly postal surveys.\n at baseline both groups were well matched in their physical performance, health and activity levels. The intervention subjects attended a median of 23 exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures; postural sway on the floor with eyes open and eyes closed and coordinated stability. The groups did not differ at retest in measures of strength, reaction time and walking speed or on Short-Form 36, Physical Activity Scale for the Elderly or fear of falling scales. Within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group (IRR=0.60, 95% CI 0.36-0.99).\n these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people.", "Falls occur mainly while walking or performing concurrent tasks. We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals.\n We conducted a 12-month randomized controlled trial involving 134 community-dwelling individuals older than 65 years, who are at increased risk of falling. They were randomly assigned to an intervention group (n = 66) or a delayed intervention control group scheduled to start the program 6 months later (n = 68). The intervention was a 6-month multitask exercise program performed to the rhythm of piano music. Change in gait variability under dual-task condition from baseline to 6 months was the primary end point. Secondary outcomes included changes in balance, functional performances, and fall risk.\n At 6 months, there was a reduction in stride length variability (adjusted mean difference, -1.4%; P < .002) under dual-task condition in the intervention group, compared with the delayed intervention control group. Balance and functional tests improved compared with the control group. There were fewer falls in the intervention group (incidence rate ratio, 0.46; 95% confidence interval, 0.27-0.79) and a lower risk of falling (relative risk, 0.61; 95% confidence interval, 0.39-0.96). Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention. The benefit of the intervention on gait variability persisted 6 months later.\n In community-dwelling older people at increased risk of falling, a 6-month music-based multitask exercise program improved gait under dual-task condition, improved balance, and reduced both the rate of falls and the risk of falling. Trial Registration clinicaltrials.gov Identifier: NCT01107288.", "To evaluate the effectiveness of an enhanced balance training program in improving mobility and well-being of elderly people with balance problems.\n Prospective, single-blind, randomized, controlled trial.\n District general hospital.\n One hundred ninety-nine patients aged 60 and older with a Berg Balance Scale (BBS) score of less than 45.\n Six weeks enhanced balance training consisting of a series of repetitive tasks of increasing difficulty specific to functional balance. The control group received physiotherapy conforming to existing practice in elderly patients with mobility problems.\n Ten-meter timed walk test (TWT), BBS, Frenchay Activities Index (FAI), Falls Handicap Inventory (FHI), and European Quality of Life questionnaire (Euroqol) measured at 6, 12, and 24 weeks after intervention.\n The mean age +/- standard deviation of subjects was 82.7 +/- 5.6, and baseline characteristics were comparable between the groups. Both groups showed improvements in TWT (intervention: 22.5-16.5 seconds, P =.001; control: 20.5-15.8 seconds, P =.054), BBS (intervention: 33.3-42.7, P =.001; control: 33.4-42.0, P <.0001), FAI (18-21, P =.02 in both groups), FHI score (intervention: 31-17, P =.0001; control: 33-17, P =.0001) and Euroqol score (intervention: 58-65, P =.04; control: 60-65, P =.07). There were no intergroup differences at any time. More patients reported increased confidence in walking indoors (36% vs 28%; P =.04) and outdoors (27% vs 18%; P =.02) in the enhanced balance-training group.\n Exercise programs significantly improve balance and mobility in patients with balance problems, independent of strategy. Enhanced balance training may, in addition, improve confidence and quality of life but needs further investigation.", "The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength, exercise capacity, gait and balance of deconditioned male nursing home residents. Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale, who demonstrated less than 80% of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled. Subjects were randomized to either an exercise (n = 8) or a control (n = 6) group. All participants underwent an exercise test to determine maximal oxygen uptake (VO2max) and received quantitative gait and balance measurements. The subjects assigned to the exercise group than completed a 12-wk program of weight training for the lower extremities and stationary cycling. Both the exercise and control groups were then retested. Ten outcome variables were assessed: Tinetti mobility scores, VO2max, isokinetic-tested lower extremity strength and endurance, stride length, gait velocity, stance time, gait duration, cadence and balance. The exercise group, after completion of the program, demonstrated significant improvements in Tinetti mobility scores (P < 0.05), combined right and left quadricep muscle strength (P < 0.01), right and left lower extremity muscular endurance (P < 0.01), left stride length and gait velocity (P < 0.05), although other outcome variables changed insignificantly. The control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength (P < 0.05). Nevertheless, for those outcome variables that had improved significantly in the exercise group, the changes amounted to only a 5 to 10% increase over the baseline measurements. These findings showed that an appropriately designed high intensity exercise program can result in significant although limited improvements for clinical mobility scores, strength, muscular endurance and certain gait parameters.", "This study tested the hypothesis that a home-based exercise program would improve functional performance in elderly people.\n We conducted a 6-month, single-blinded, randomized controlled trial. 72 community dwelling men and women (aged >/=70 years) with self-reported and laboratory-based functional impairment were recruited for the study. Participants were randomly assigned to either a home-based progressive strength, balance, and general physical activity intervention or an attention-control group that received home-based nutrition education. Functional performance was measured in the laboratory using the Physical Performance Test (PPT) and the Established Populations for Epidemiologic Studies of the Elderly (EPESE) short physical performance battery. Physiologic capacity was measured by strength (one repetition maximum), dynamic balance (tandem walk), gait speed (2-meter walk), and cardiovascular endurance (6-minute walk).\n 70 participants (97%) completed the 6-month trial. Compliance with study interventions within each group ranged from 75% in controls to 82% in exercisers. PPT increased by 6.1 +/- 13.4% in exercisers and decreased by 2.8 +/- 13.6% in controls (p =.02). EPESE improved by 26.2 +/- 37.5% in exercisers and decreased by 1.2 +/- 22.1% in controls (p =.001). Dynamic balance improved by 33.8 +/- 14.4% in exercisers versus 11.5 +/- 23.7% in controls (p =.0002). There were no differences between groups in the change in strength, gait speed, or cardiovascular endurance.\n Minimally supervised exercise is safe and can improve functional performance in elderly individuals. The improvements in functional performance occurred along with improvements in balance but without a significant change in muscle strength or endurance.", "To examine the effects of a community-based group exercise program for older individuals with chronic stroke.\n Prospective, single-blind, randomized, controlled intervention trial.\n Intervention was community-based. Data collection was performed in a research laboratory located in a rehabilitation hospital.\n Sixty-three older individuals (aged > or = 50) with chronic stroke (poststroke duration > or = 1 year) who were living in the community.\n Participants were randomized into intervention group (n=32) or control group (n=31). The intervention group underwent a fitness and mobility exercise (FAME) program designed to improve cardiorespiratory fitness, mobility, leg muscle strength, balance, and hip bone mineral density (BMD) (1-hour sessions, three sessions/week, for 19 weeks). The control group underwent a seated upper extremity program.\n Cardiorespiratory fitness (maximal oxygen consumption), mobility (6-minute walk test), leg muscle strength (isometric knee extension), balance (Berg Balance Scale), activity and participation (Physical Activity Scale for Individuals with Physical Disabilities), and femoral neck BMD (using dual-energy x-ray absorptiometry).\n The intervention group had significantly more gains in cardiorespiratory fitness, mobility, and paretic leg muscle strength than controls. Femoral neck BMD of the paretic leg was maintained in the intervention group, whereas a significant decline of the same occurred in controls. There was no significant time-by-group interaction for balance, activity and participation, nonparetic leg muscle strength, or nonparetic femoral neck BMD.\n The FAME program is feasible and beneficial for improving some of the secondary complications resulting from physical inactivity in older adults living with stroke. It may serve as a good model of a community-based fitness program for preventing secondary diseases in older adults living with chronic conditions.", "Age-related changes in the ability to adjust to alterations in sensory information contribute to impaired postural stability. The purpose of this randomized controlled trial was to investigate the effect of sensory-specific balance training on proprioceptive reintegration.\n The subjects of this study were 36 older participants who were healthy.\n Participants were randomly assigned to a balance exercise group (n=17) or a falls prevention education group (n=19). The primary outcome measure was the center-of-pressure (COP) velocity change score. This score represented the difference between COP velocity over 45 seconds of quiet standing and each of six 5-second intervals following proprioceptive perturbation through vibration with or without a secondary cognitive task. Clinical outcome measures included the Fullerton Advanced Balance (FAB) Scale and the Activities-specific Balance Confidence (ABC) Scale. Assessments were conducted at baseline, postintervention, and at an 8-week follow-up.\n Following the exercise intervention, there was less destabilization within the first 5 seconds following vibration with or without a secondary task than there was at baseline or in the falls prevention education group. These training effects were not maintained at the 8-week follow-up. Postintervention improvements also were seen on the FAB Scale and were maintained at follow-up. No changes in ABC Scale scores were identified in the balance exercise group, but ABC Scale scores indicated reduced balance confidence in the falls prevention education group postintervention.\n The results of this study support short-term enhanced postural responses to proprioceptive reintegration following a sensory-specific balance exercise program.", "older people participate in exercise programmes to reduce the risk of falls but no study has investigated a specific balance strategy training intervention presented in a workstation format for small groups.\n to determine whether a specific balance strategy training programmeme delivered in a workstation format was superior to a community based exercise class programme for reducing falls.\n a randomised controlled trial model.\n Neurological Disorders, Ageing and Balance Clinic, Department of Physiotherapy, The University of Queensland.\n 73 males and females over 60 years, living independently in the community and who had fallen in the previous year were recruited.\n all subjects received a falls risk education booklet and completed an incident calendar for the duration of the study. Treatment sessions were once a week for 10 weeks. Subject assessment before and after intervention and at 3 months follow-up included number of falls, co-morbidities, medications, community services and activity level, functional motor ability, clinical and laboratory balance measures and fear of falling.\n all participants significantly reduced the number of falls (P < 0.000). The specific balance strategy intervention group showed significantly more improvement in functional measures than the control group (P = 0.034). Separate group analyses indicated significantly improved performance in functional motor ability and most clinical balance measures for the balance group (P < 0.04). The control group only improved in TUG and TUGcog.\n the results provide evidence that all participants achieved a significant reduction in falls. Specific balance strategy training using workstations is superior to traditional exercise classes for improving function and balance.", "The purpose of this randomized controlled trial was to measure the effectiveness of A Matter of Balance, a small-group based balance program, on muscle strength, gait, balance, and fall risk among older community-dwelling adults at risk for falls. A secondary aim was to measure the effects of the program on actual fall rates over the 3-month study.\n Twenty-three older adults were randomly assigned to either an experimental group that participated in a 12-week small-group based balance program or a control group. Subjects were assessed at baseline and following an intervention using the following outcome measures: lower extremity manual muscle testing (MMT) and range of motion; gait analysis on the GAITRite system; balance parameters on the SMART EquiTest, the Timed Up and Go test, the Berg Balance Scale, and incidence of falls.\n A repeated measures ANOVA revealed that there was a significant interaction between groups over time in the Berg Balance Scale scores, P < or = .05. The experimental group improved over time (48.1 to 52.9/56, respectively), whereas the control group decreased in performance (49.1 to 47.8/56, respectively), P < or = .05. The mean number of falls was significantly less in the experimental group during the intervention compared with the control group (0.09 and 0.50, respectively), P < or = .05.\n A community-based multifactorial intervention including individualized fall risk assessment, exercise, and home assessment appears to safely and effectively reduce the number of falls, resulting in significant improvements in functional balance ability and decreased fall risk.", "Visual feedback related to weight distribution and center-of-pressure positioning has been shown to be effective in increasing stance symmetry following stroke, although it is not clear whether functional balance ability also improves. This study compared the relative effectiveness of visual feedback training of center-of-gravity (CoG) positioning with conventional physical therapy following acute stroke.\n Forty-six people who had strokes within 80 days before the study, resulting in unilateral hemiparesis, and who were in need of balance retraining participated.\n Initially, subjects were randomly assigned to visual feedback or conventional physical therapy groups for balance retraining until 16 subjects per group were recruited. The next 14 subjects were assigned to a control group. All subjects received physical therapy and occupational therapy (regular therapy) 2 hours a day, and subjects in the 2 experimental groups received additional balance training 30 minutes a day until discharge. The visual feedback group received information about their CoG position as they shifted their weight during various activities. The conventional therapy group received verbal and tactile cues to encourage symmetrical stance and weight shifting. Static (postural sway) and activity-based measures of balance (Berg Balance Scale, gait speed, and the Timed \"Up & Go\" Test) were contrasted across the 3 groups at baseline, at discharge, and at 1 month following discharge using an analysis of variance for repeated measures.\n All groups demonstrated marked improvement over time for all measures of balance ability, with the greatest improvements occurring in the period from baseline to discharge. No between-group differences were detected in any of the outcome measures.\n Visual feedback or conventional balance training in addition to regular therapy affords no added benefit when offered in the early stages of rehabilitation following stroke.", "Exercise as a falls prevention strategy is more complex with people at risk than with the general population. The Lifestyle approach to reducing Falls through Exercise (LiFE) involves embedding balance and lower limb strength training in habitual daily routines.\n A total of 34 community-residing people aged ≥70 years were randomised either into the LiFE programme or into a no-intervention control group and followed up for six months. Inclusion criteria were two or more falls or an injurious fall in the past year.\n There were 12 falls in the intervention group and 35 in the control group. Therelative risk (RR) analysis demonstrated a significant reduction in falls (RR = 0.23; 0.07-0.83). There were indications that dynamic balance (P = 0.04 at three months) and efficacy beliefs (P = 0.04 at six months) improved for the LiFE programme participants. In general, secondary physical and health status outcomes, which were hypothesised as potential mediators of fall risk, improved minimally and inconsistently.\n LiFE was effective in reducing recurrent falls in this at-risk sample. However, there were minimal changes in secondary measures. The study was feasible in terms of recruitment, randomisation, blinding and data collection. A larger randomised trial is needed to investigate long-term efficacy, mechanisms of benefit and clinical significance of this new intervention.", "To determine the effects of a perturbed walking exercise using a bilateral separated treadmill in physically disabled elderly.\n Participants of the study were 32 long-term care facility residents and outpatients aged 66-98 yrs. Participants were randomly assigned to a usual exercise group or to a treadmill exercise group. Perturbed gait exercise on a treadmill continued for 6 mos. Number of falls and time to first fall during a 6-mo period, balance and gait functions, and reaction time were evaluated before and after intervention.\n The treadmill exercise group showed significant improvement in balance and reaction time when compared with the usual exercise group. Number of falls in the treadmill exercise group was 21% lower than that in the usual exercise group. However, this difference was not significant. No significant differences were seen in time to first fall.\n Gait training with unexpected perturbation seems to have a beneficial impact on physical function in disabled elderly individuals. The results suggest that this program may be used as an exercise intervention to reduce falls in institutional settings.", "To compare the effectiveness of unsupervised home and supervised group exercise on parameters related to risk of falling among older adults.\n Prospective, single-blind, randomized and controlled trial.\n Nursing home.\n The subjects were selected from 535 independent individuals who resided in a nursing home. Forty-two older adults, aged > 65 years, with risk of falling were recruited, and 32 of them completed the study.\n The 42 subjects were divided into two groups (unsupervised home exercise and supervised exercise group) randomly. Exercise sessions were performed three times a week for a period of eight weeks.\n Measurements were taken at baseline and after the completion of the exercise programme. The fear of falling was evaluated using a visual analogue scale, quadriceps muscle strength was measured with a dynamometer, flexibility was assessed with the sit and reach test, functional mobility was determined using the Timed Up and Go Test, balance was evaluated using one-leg and tandem standing, and Berg Balance Scale and proprioception was assessed with knee position sense.\n Thirty-two subjects (unsupervised home exercise n = 15, supervised group exercise n = 17) completed the exercise programme and all of the measurements. The unsupervised home exercise group showed significant improvement in balance, functional mobility and flexibility (P > 0.05). In addition to balance, functional mobility and flexibility, the supervised exercise group also showed significant improvements in both strength and proprioception (P > 0.05).\n Supervised group exercise is more effective at reducing the risk factors related to falling among older adults living in a nursing home than is unsupervised home exercise.", "The majority of patients after a hip fracture do not return to prefracture functional status. Depression has been shown to affect recovery. Although exercise can reduce impairments, access issues limit elderly people from participating in facility-based programs. The primary purpose of this study was to determine the effects and feasibility of a home exercise program of moderate- or high-intensity exercise. A secondary purpose was to explore the relationship of depression and physical recovery.\n Thirty-three elderly people (24 women, 9 men; mean = 78.6 years of age, SD = 6.8, range = 64-89) who had completed a regimen of physical therapy following hip fracture participated in the study. Subjects were randomly assigned to a resistance training group, an aerobic training group, or a control group.\n Subjects were tested before and upon completion of the exercise trial. Isometric lower-extremity force, 6-minute-walk distance, free gait speed, mental status, and physical function were measured. Each exercise session was supervised by a physical therapist, and subjects received 20 visits over 12 weeks. The control group received biweekly mailings. The resistance training group performed 3 sets of 8 repetitions at the 8-repetition maximum intensity using a portable progressive resistance exercise machine. The aerobic training group performed activities that increased heart rate 65% to 75% of their age-predicted maximum for 20 continuous minutes.\n Resistance and aerobic training were performed without apparent adverse effects, and adherence was 98%. All groups improved in distance walked, force produced, gait speed, and physical function. Isometric force improved to a greater extent in the intervention groups than in the control group. Depressive symptoms interacted with treatment group in explaining the outcomes of 6-minute-walk distance and gait speed.\n High-intensity exercise performed in the home is feasible for people with hip fracture. Larger sample sizes may be necessary to determine whether the exercise regimen is effective in reducing impairments and improving function. Depression may play a role in the level of improvement attained.", "BACKGROUND and\n Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used.\n Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients' physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function.\n Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.\n This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.", "This study compared the efficacy of 16 weeks of either resistance training, aerobic walking, or combined resistance training and aerobic walking on the performance of functional tasks among adults age 65 years and older with limited functional ability. One hundred thirty-one older adult individuals were randomized into four groups: resistance training, aerobic walking, combined resistance and aerobic walking groups, or a nonexercise control group. Each of the exercise groups documented 70% compliance with their respective exercise intervention, which included three weekly exercise sessions. At baseline, and 8 and 16 weeks following baseline, all participants completed six assessments of their functional ability. Analysis of covariance indicated that all three exercise intervention groups significantly improved measures of functional ability, with the resistance group demonstrating the most consistent gains over the six measures. These findings indicate that older adults who are functionally limited can improve their functional ability through a variety of types of exercise.", "The study tested the effect of strength and endurance training on gait, balance, physical health status, fall risk, and health services use in older adults.\n The study was a single-blinded, randomized controlled trial with intention-to-treat analysis. Adults (n = 105) age 68-85 with at least mild deficits in strength and balance were selected from a random sample of enrollees in a health maintenance organization. The intervention was supervised exercise (1-h sessions, three per week, for 24-26 weeks), followed by self-supervised exercise. Exercise groups included strength training using weight machines (n = 25), endurance training using bicycles (n = 25), and strength and endurance training (n = 25). Study outcomes included gait tests, balance tests, physical health status measures, self-reported falls (up to 25 months of follow-up), and inpatient and outpatient use and costs.\n There were no effects of exercise on gait, balance, or physical health status. Exercise had a protective effect on risk of falling (relative hazard = .53, 95% CI = .30-.91). Between 7 and 18 months after randomization, control subjects had more outpatient clinic visits (p < .06) and were more likely to sustain hospital costs over $5000 (p < .05).\n Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults. In community-living adults with mainly mild impairments in gait, balance, and physical health status, short-term exercise may not have a restorative effect on these impairments.", "Aging compromises the ability of the central nervous system to maintain body balance and reduces the capacity for adaptive reactions. To prevent falls, the reception conditions for sensory information need to be improved.\n To evaluate the impact of a structured aquatic and a non-aquatic exercise program for lower-limb muscle endurance on the static and dynamic balance of elderly people.\n This was a prospective randomized clinical study in which the variables were assessed before and after the training program. Thirty-six elderly people were evaluated using four tests: the Berg Balance Scale, Dynamic Gait Index, gait speed and tandem gait. The participants were randomized into three groups: aquatic exercise group, non-aquatic exercise group and control group. The exercise groups underwent a program for lower-limb muscle endurance that consisted of 40-minute sessions twice a week for six weeks. The participants were reevaluated after six weeks. The data were analyzed statistically using the univariate ANOVA test for comparisons between the groups before and after the intervention.\n The program for lower-limb muscle endurance significantly increased balance (p<0.05) in the evaluation tests after the training program.\n The muscle endurance program provided a significant improvement in static and dynamic balance among community-dwelling elderly people. It was also possible to infer that this improvement occurred regardless of the environment, i.e. aquatic or non-aquatic. Article registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under the number ACTRN 12609000780257.", "To analyse the effects of two interventions on the cognition and balance of institutionalized elderly people with mixed dementia.\n Fifty-four participants were allocated into three groups. Group 1 was assisted by an interdisciplinary programme comprising physiotherapy, occupational therapy and physical education. A physiotherapist alone carried out the intervention in group 2. Group 3 was considered as control. Assessors were blinded to guarantee the absence of bias. Cognitive functions were analysed with the Mini-Mental State Examination and the Brief Cognitive Screening Battery. Balance was assessed with the Berg Balance Scale and the Timed Get-Up-and-Go Test. Multiple analysis of variance (MANOVA) was used to test possible main effects of the interventions.\n The results showed benefits on the balance of subjects in both groups 1 (F=3.9, P<0.05) and 2 (F=3.1, P<0.05), compared with group 3. MANOVA did not indicate benefits on the cognitive functions between groups 1 and 3 (F=1.1, P>0.05) and groups 2 and 3 (F=1.6, P>0.05). However, univariate analysis indicated some benefits of the interdisciplinary intervention on two specific domains measured by the Brief Cognitive Screening Battery (F=26.5, P<0.05; F=4.4, P<0.05).\n Six months of multidisciplinary or physiotherapeutic intervention were able to improve a person's balance. Although global cognition did not improve through treatment, when the intervention was carried out on a multidisciplinary basis we observed an attenuation in the decline of global cognition on two specific cognitive domains. Exercises applied in different contexts may have positive outcomes for people with dementia.", "Summary: This study showed that combination of strength, balance, agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women. The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems.\n This 1-year randomized, controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women.\n One hundred and forty-nine healthy women aged 70-78 years were randomly assigned into: group 1-resistance training (RES), group 2-balance-jumping training (BAL), group 3-combination of resistance and balance-jumping training (COMB), and group 4-controls (CON). Self-rated physical functioning, leg extensor force, dynamic balance, and bone mass and structure were measured.\n Self-rated physical functioning improved in the COMB group, but was reduced in the CON group; the mean inter-group difference was 10% (95% CI: 0-22%). Mean increase in the leg extensor force was higher in the RES (14%; 4-25%) and COMB (13%; 3-25%) compared with the CON groups. Dynamic balance improved in the BAL (6%; 1-11%) and in the COMB (8%; 3-12%) groups. There were no inter-group differences in BMC at the proximal femur. In those COMB women who trained at least twice a week, the tibial shaft structure weakened 2% (0-4%) less than those in the CON group.\n Strength, balance, agility, and jumping training (especially in combination) prevented functional decline in home-dwelling elderly women. In addition, positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility.", "To determine the effect of two different community-based group exercise programs on functional balance, mobility, postural reflexes, and falls in older adults with chronic stroke.\n A randomized, clinical trial.\n Community center.\n Sixty-one community-dwelling older adults with chronic stroke.\n Participants were randomly assigned to an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both groups exercised three times a week for 10 weeks.\n Participants were assessed before, immediately after, and 1 month after the intervention for Berg Balance, Timed Up and Go, step reaction time, Activities-specific Balance Confidence, and Nottingham Health Profile. Testing of standing postural reflexes and induced falls evoked by a translating platform was also performed. In addition, falls in the community were tracked for 1 year from the start of the interventions.\n Although exercise led to improvements in all clinical outcome measures for both groups, the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group. In addition, the agility group experienced fewer induced falls on the platform.\n Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes, functional balance, and mobility and may lead to a reduction of falls in older adults with stroke.", "To compare the effects of weight-bearing and non-weight-bearing home exercise programs and a control program on physical ability (strength, balance, gait, functional performance) in older people who have had a hip fracture.\n Randomized controlled trial with 4-month follow-up.\n Australian community-dwellers (82%) and residents of aged care facilities who had completed usual care after a fall-related hip fracture.\n One hundred twenty older people entered the trial, 40 per group (average age +/- standard deviation, 79+/-9y) and 90% completed the 4-month retest.\n Home exercise prescribed by a physical therapist.\n Strength, balance, gait, and functional performance.\n At the 4-month retest, there were differences between the groups in the extent of improvement since the initial assessment for balance (F(10,196)=2.82, P<.001) and functional performance (F(6,200)=3.57, P<.001), but not for strength (F(12,190)=1.09, P=.37) or gait (F(8,200)=.39, P=.92). The weight-bearing exercise group showed the greatest improvements in measures of balance and functional performance (between-group differences of 30%-40% of initial values).\n A weight-bearing home exercise program can improve balance and functional ability to a greater extent than a non-weight-bearing program or no intervention among older people who have completed usual care after a fall-related hip fracture.", "To determine the safety and efficacy of 3 months of resistive training of multiple lower extremity muscle groups compared with balance training in persons over 75 years.\n Randomized 3-month clinical trial. Subjects (n = 110, mean age 80) were randomized to 4 groups in a 2 x 2 design (control, resistive, balance, combined resistive/balance).\n Resistive training involved knee extension and flexion, hip abduction and extension, and plantar and dorsiflexion using simple resistive machines and sandbags. Balance training consisted of exercises to improve postural control. The control group attended 5 health-related discussion sessions.\n Summed isokinetic moments (N m) of 8 leg movements: hip, knee and ankle flexion/extension, and hip abduction/adduction. Secondary outcomes were gait velocity and chair rise time.\n Summed peak moment increased in both resistive exercise-trained groups (13% increase in the resistive group and 21% in the combined training group, P < 0.001). The effect of resistance training was significant (MANOVA F = 21.1, P < 0.001), but balance training did not improve strength, and there was no interaction (positive or negative) between balance and resistive training. Maximal gait velocity and chair rise time did not improve. Eleven subjects (20%) had musculoskeletal complaints related to resistive training, but all were able to complete the program with modifications.\n Resistive training using simple equipment is an effective and acceptable method to increase overall leg strength in older persons. Resistive or balance training did not improve maximal gait velocity or chair rise time in this sample of relatively healthy older persons.", "To determine the effects of moderate intensity group-exercise programs on falls, functional performance, and disability in older adults; and to investigate the influence of frailty on these effects.\n A 20-week, multicenter randomized controlled trial, with 52-week follow-up.\n Fifteen homes for the elderly.\n Two hundred seventy-eight men and women (mean age +/- standard deviation, 85+/-6y).\n Two exercise programs were randomly distributed across 15 homes. The first program, functional walking (FW), consisted of exercises related to daily mobility activities. In the second program, in balance (IB), exercises were inspired by the principles of Tai Chi. Within each home participants were randomly assigned to an intervention or a control group. Participants in the control groups were asked not to change their usual pattern of activities. The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks.\n Falls, Performance Oriented Mobility Assessment (POMA), physical performance score, and the Groningen Activity Restriction Scale (GARS) (measuring self-reported disability).\n Fall incidence rate was higher in the FW group (3.3 falls/y) compared with the IB (2.4 falls/y) and control (2.5 falls/y) groups, but this difference was not statistically significant. The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail (hazard ratio [HR] = 2.95; 95% confidence interval [CI], 1.64-5.32). For participants who were classified as being pre-frail, the risk of becoming a faller decreased; this effect became significant after 11 weeks of training (HR = .39; 95% CI, .18-.88). Participants in both exercise groups showed a small, but significant improvement in their POMA and physical performance scores. In the FW group, this held true for the GARS score as well. Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores.\n Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail, but not in frail elderly.", "To examine the effectiveness of a dual-task-based exercise program on walking ability in subjects with chronic stroke.\n Single-blind randomized controlled trial.\n General community.\n Twenty-five subjects with chronic stroke who were at least limited community ambulatory subjects (a minimum gait velocity, 58cm/s).\n Participants were randomized into a control group (n=12) or experimental group (n=13). Subjects in the control group did not receive any rehabilitation training. Subjects in the experimental group underwent a 4-week ball exercise program.\n Gait performance was measured under single task (preferred walking) and tray-carrying task. Gait parameters of interest were walking speed, cadence, stride time, stride length, and temporal symmetry index.\n The experimental group showed significant improvement in all selected gait measures except for temporal symmetry index under both task conditions. In the control group, there were no significant changes over the 4-week period for all selected measures. There was a significant difference between groups for all selected gait variables except for temporal symmetry index under both task conditions.\n The dual-task-based exercise program is feasible and beneficial for improving walking ability in subjects with chronic stroke.", "To evaluate the effects of two exercise approaches, Tai Chi (TC) and computerized balance training (BT), on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls).\n The Atlanta FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques), a prospective, randomized, controlled clinical trial with three arms (TC, BT, and education [ED]. Intervention length was 15 weeks, with primary outcomes measured before and after intervention and at 4-month follow-up. Falls were monitored continuously throughout the study.\n Persons aged 70 and older living in the community.\n A total of 200 participants, 162 women and 38 men; mean age was 76.2.\n Biomedical (strength, flexibility, cardiovascular endurance, body composition), functional (IADL), and psychosocial well-being (CES-D scale, fear of falling questionnaire, self-perception of present and future health, mastery index, perceived quality of sleep, and intrusiveness) variables.\n Grip strength declined in all groups, and lower extremity range of motion showed limited but statistically significant changes. Lowered blood pressure before and after a 12-minute walk was seen following TC participation. Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group (P = .046 and P = .058, respectively). After adjusting for fall risk factors, TC was found to reduce the risk of multiple falls by 47.5%.\n A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty. This intervention can also have favorable effects upon the occurrence of falls. Tai Chi warrants further study as an exercise treatment to improve the health of older people.", "To evaluate the efficacy of a task-oriented walking intervention in improving balance self-efficacy in persons with stroke and to determine whether effects were task-specific, influenced by baseline level of self-efficacy and associated with changes in walking and balance capacity.\n Secondary analysis of a two-center, observer-blinded, randomized, controlled trial.\n General community.\n Ninety-one individuals with a residual walking deficit within 1 year of a first or recurrent stroke.\n Task-oriented interventions targeting walking or upper extremity (UE) function were provided three times a week for 6 weeks.\n Activities-specific Balance Confidence Scale, Six-Minute Walk Test, 5-m walk, Berg Balance Scale, and Timed \"Up and Go\" administered at baseline and postintervention.\n The walking intervention was associated with a significantly greater average proportional change in balance self-efficacy than the UE intervention. Treatment effects were largest in persons with low self-efficacy at baseline and for activities relating to tasks practiced. In the walking group, change in balance self-efficacy correlated with change in functional walking capacity (correlation coefficient=0.45, 95% confidence interval=0.16-0.68). Results of multivariable modeling suggested effect modification by the baseline level of depressive symptoms and a prognostic influence of age, sex, comorbidity, time poststroke, and functional mobility on change in self-efficacy.\n Task-oriented walking retraining enhances balance self-efficacy in community-dwelling individuals with chronic stroke. Benefits may be partially the result of improvement in walking capacity. The influence of baseline level of self-efficacy, depressive symptoms, and prognostic variables on treatment effects are of clinical importance and must be verified in future studies.", "This randomized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength, endurance, mobility, and fall rates in fall-prone elderly men with chronic impairments.\n Fifty-nine community-living men (mean age = 74 years) with specific fall risk factors (i.e., leg weakness, impaired gait or balance, previous falls) were randomly assigned to a control group (n = 28) or to a 12-week group exercise program (n = 31). Exercise sessions (90 minutes, three times per week) focused on increasing strength and endurance and improving mobility and balance. Outcome measures included isokinetic strength and endurance, five physical performance measures, and self-reported physical functioning, health perception, activity level, and falls.\n Exercisers showed significant improvement in measures of endurance and gait. Isokinetic endurance increased 21% for right knee flexion and 26% for extension. Exercisers had a 10% increase (p < .05) in distance walked in six minutes, and improved (p < .05) scores on an observational gait scale. Isokinetic strength improved only for right knee flexion. Exercise achieved no significant effect on hip or ankle strength, balance, self-reported physical functioning, or number of falls. Activity level increased within the exercise group. When fall rates were adjusted for activity level, the exercisers had a lower 3-month fall rate than controls (6 falls/1000 hours of activity vs 16.2 falls/1000 hours, p < .05).\n These findings suggest that exercise can improve endurance, strength, gait, and function in chronically impaired, fall-prone elderly persons. In addition, increased physical activity was associated with reduced fall rates when adjusted for level of activity.", "This study tested whether a 12-week dynamic resistance strength training program can change gait velocity and improve measures of balance among adults age 65 and older. Fifty-five community-dwelling adults (mean age = 71.1) were randomized into an exercise (n = 25) or control (n = 30) group. The exercisers were requested to complete three bouts of strength training per week for 12 weeks using elastic tubing. At posttest the exercisers demonstrated slower gait velocity, enhanced balance, and an improved ability to walk backward, although none of these posttest measures was significantly different from the control group.", "Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be \"prescribed\" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis.\n We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry).\n Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06).\n Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.", "Balance training programs have not shown consistent results among older adults, and it remains unclear how different training methods can be adapted to frail elderly people.\n The purpose of this study was to investigate the effects of a 4-week visual feedback-based balance training on the postural control of frail elderly women living in residential care homes.\n Elderly women of two residential care facilities were randomized to an exercise group (EG, n = 20) and to a control group (CG, n = 7). The EG participated in training sessions three times/week for 4 weeks. The exercises were carried out with a computerized force platform with visual feedback screen. The dimensions of balance function studied were standing body sway, dynamic weight shifting, and Berg Balance Scale performance.\n The EG showed significant improvement in balance functions. The performance time in dynamic balance tests improved on average by 35.9% compared with a 0.6% increase in the CG (p = 0.025-0.193). The performance distance in these tests decreased on average by 28.2% in the EG as compared with a 9.8% decrease seen in the CG. The Berg Balance Scale performance improved by 6.9% compared with a 0.7% increase in the CG (p = 0.003). The standing balance tests in the more demanding standing positions showed improvements in the EG, whereas similar changes in the CG were not found.\n Our findings suggest that balance training based on visual feedback improves the balance control in frail elderly women living in residential care, also enhancing the performance of functional balancing tasks relevant to daily living. The subjects were motivated to participate in the training, as indicated by the high compliance (97.5%) with the program.\n Copyright 2004 S. Karger AG, Basel", "The knowledge concerning balance training actually lowering fall rates among frail older persons is limited.\n The aim of this study was to examine the effects of a 4-week individualized visual feedback-based balance training on the fall incidence during 1-year follow-up among frail older women living in residential care.\n Twenty-seven older women from 2 residential care homes were randomized into exercise (n = 20) and control (n = 7) groups. Balance measurements were carried out before and after a 4-week training period and falls were monitored by monthly diaries for 1 year. An interview about fear of falling and physical activity was completed before and after the intervention and after the 1-year follow-up.\n A positive effect of balance training on fall incidence was found. A dynamic Poisson regression model showed that during the follow-up the monthly risk of falling was decreased in the exercise group compared to controls (risk ratio 0.398, 95% CI 0.174-0.911, p = 0.029). In addition, the exercise group reported a reduced fear of falling and increased physical activity after a training period but these changes declined during the follow-up period.\n Individualized visual feedback-based balance training was shown to be a promising method for fall prevention among frail older women. High compliance (97.5%) with the training program showed that carefully targeted training programs can be carried out among older people with health limitations.\n Copyright 2004 S. Karger AG, Basel.", "To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls.\n A randomized controlled 3-month intervention trial, with an additional 3-month follow-up.\n Out-patient geriatric rehabilitation unit.\n Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture.\n Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded.\n Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3).\n No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3-month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245).\n Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls.", "There are few studies published that combine the interventions of physical training and nutrition. The aim of the present study was to describe the impact of a physical and nutritional intervention program for frail community- dwelling elderly people over the age of 75.\n Ninety-six community-dwelling elderly people (58 women) were randomized to four different groups: i) a physical training program (aerobic, muscle strength, balance), ii) a nutritional intervention program (individually targeted advice and group sessions), iii) a combination of these interventions, and iv) a control group. At baseline subjects were screened for physical performance such as muscle strength, balance, mobility and activities of daily living, as well as nutritional aspects such as energy intake, body weight and fat-free mass. These measurements were repeated immediately after the intervention, which lasted for 12 weeks, and after another 6 months.\n The intention-to-treat analysis indicated significant improvements in lower- extremity muscle strength in both training groups compared with the nutrition group at 1st follow-up. There were small significant changes for some of the balance measurements in the training group without nutrition treatment. The nutrition intervention did not show any significant results.\n This study shows the positive effect on lower-extremity muscle strength directly after the intervention. Balance training most probably needs to be more individualized in order to be effective for frail elderly people. Further studies are needed, with larger sample sizes, to investigate the effects of these types of interventions before any further conclusions can be drawn.", "To compare the effects of whole body vibration (WBV) and conventional physiotherapy (PT) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson's disease (PD).\n Randomized controlled rater-blinded trial comparing 2 active interventions, final follow-up assessment 4 weeks after termination of active intervention.\n Specialized referral center, hospitalized care.\n Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication (N=27) were randomized (intent-to-treat population) to receive WBV (n=13) or conventional PT (controls, n=14). Twenty-one patients (per protocol population) completed follow-up (14 men, 7 women; mean age, 73.8 y; age range, 62-84 y; mean disease duration, 7.2 y; mean dopa-equivalent dose, 768 mg/d).\n Subjects were randomized to receive 30 sessions (two 15-min sessions a day, 5 days a week) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board. Twenty-one subjects (10 with WBV, 11 controls) were available for follow-up 4 weeks after treatment termination.\n The primary measure was Tinetti Balance Scale score. Secondary clinical ratings included stand-walk-sit test, walking velocity, Unified Parkinson's Disease Rating Scale (section III motor examination) score, performance in the pull test, and dynamic posturography.\n The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls. All secondary measures, except posturography, likewise improved at follow-up compared with baseline in both groups. Quantitative dynamic posturography only improved in patients with WBV (1937-1467 mm) whereas there was no significant change in controls (1832-2030 mm).\n Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program. There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training.", "Among elderly persons, falls account for 87% of all fractures and are contributing factors in many nursing home admissions. This study evaluated the effect of an easily implemented, low-intensity exercise program on the incidence of falls and the time to first fall among a clinically defined population of elderly men and women.\n This community-based, randomized trial compared the exercise intervention with a no-intervention control. The participants were 294 men and women, aged 60 years or older, who had either a hospital admission or bed rest for 2 days or more within the previous month. Exercise participants were scheduled to attend exercise sessions lasting 45 minutes, including warm-up and cool-down, 3 times a week for 8 weeks (24 sessions). Assessments included gait and balance measures, self-reported physical function, the number of medications being taking at baseline, participant age, sex, and history of falling. Falls were tracked for 1 year after each participant's baseline assessment.\n 29% of the study participants reported a fall during the study period. The effect of exercise in preventing falls varied significantly by baseline physical function level (p < or =.002). The risk for falls decreased for exercise participants with low baseline physical functioning (hazard ratio,.51) but increased for exercise participants with high baseline physical functioning (hazard ratio, 3.51).\n This easily implemented, low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations, bed rest, or both who have low levels of physical functioning.", "Decreased muscle strength impedes elders' functional performance in daily activities such as gait. The mechanisms whereby increased strength improves gait are unknown.\n A prospective, blinded, randomized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders. Lower extremity strength was measured, including hip abductor, hip extensor, and knee extensor strength. Of the 132 subjects, 120 subjects (mean age, 75.1 yrs) completed 6 months of elastic band resistance training at least 3 times a week or served as no-exercise controls.\n Subjects increased their lower extremity strength in the exercise and control groups, by 17.6% and 7.3% (p < .01), respectively. Gait stability improved significantly more in the exercise group than in the control group (p < .05). Increases in forward gait velocity were not significantly different between groups. Peak mediolateral velocity and base of support improved in the exercise group, but not in the control group. Change in lower extremity strength correlated significantly but weakly with many of the gait variables.\n Gait stability, especially mediolateral steadiness, improved in the exercise group but not in the control group. These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations.", "To primarily ascertain the effect of the Otago Exercise Program (OEP) on physiological falls risk, functional mobility, and executive functioning after 6 months in older adults with a recent history of falls and to ascertain the effect of the OEP on falls during a 1-year follow-up period.\n Randomized controlled trial.\n Dedicated falls clinics.\n Seventy-four adults aged 70 and older who presented to a healthcare professional after a fall.\n The OEP, a home-based program that consists of resistance training and balance training exercises.\n Physiological falls risk was assessed using the Physiological Profile Assessment. Functional mobility was assessed using the Timed Up and Go Test. Three central executive functions were assessed: set shifting, using the Trail Making Test Part B; updating, using the verbal digits backward test; and response inhibition, using the Stroop Color-Word Test. Falls were prospectively monitored using daily calendars.\n At 6 months, there was no significant between-group difference in physiological falls risk or functional mobility (P>or= .33). There was a significant between-group difference in response inhibition (P=.05). A falls histogram revealed two outliers. With these cases removed, using negative binomial regression, the unadjusted incidence rate ratio of falls in the OEP group compared with the control group was 0.56. The adjusted incidence rate ratio was 0.47.\n The OEP may reduce falls by improving cognitive performance.", "To compare the efficacy of seated exercises and weight-bearing (WB) exercises with social visits on fall risk factors in older people recently discharged from hospital.\n Twelve-week randomized, controlled trial.\n Home-based exercises.\n Subjects (N=180) aged 65 and older, recently discharged from hospital.\n Seated exercises (n=60), WB exercises (n=60), and social visits (n=60).\n Primary outcome factors were Physiological Profile Assessment (PPA) fall risk score, and balance while standing (Coordinated Stability and Maximal Balance Range tests). Secondary outcomes included the component parts of the PPA and other physical and psychosocial measures.\n Subjects were tested at baseline and at completion of the intervention period. After 12 weeks of interventions, subjects in the WB exercise group had significantly better performance than the social visit group on the following: PPA score (P=.048), Coordinated Stability (P<.001), Maximal Balance Range (P=.019); body sway on floor with eyes closed (P=.017); and finger-press reaction time (P=.007) tests. The seated exercise group performed better than the social visit group in PPA score (P=.019) but for no other outcome factor. The seated exercise group had the highest rate of musculoskeletal soreness.\n In older people recently discharged from the hospital, both exercise programs reduced fall risk score in older people. The WB exercises led to additional beneficial impacts for controlled leaning, reaction time, and caused less musculoskeletal soreness than the seated exercises.", "Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated.", "Resistance-training intervention studies have demonstrated meaningful health benefits in older adults; however, most have used exercises performed at specific intensities on expensive equipment, which limit their widespread applicability. We tested whether two self-paced, less expensive exercise protocols could be effective and safe for modifying neuromotor performance and functional capacity in community-dwelling adults 65-95 years of age.\n One hundred and thirty-one subjects were randomized to a novel resistance training, walking, or control group. Subjects determined their level of resistance or walking intensity (self-paced) on a session-by-session basis. Muscle strength, balance, reaction time, stair climbing speed, and a timed pen pickup task were measured before and after the intervention period. Exercisers met three times per week for 10 months.\n Significant improvements in tandem stance and single-legged stance with eyes open times and stair climbing speed were seen in both exercise groups. In addition, resistance trainers improved their muscle strength and ability to pick up an object from the floor and reduced the number of missteps taken during tandem walking, and walkers reduced tandem walking time. Controls showed no significant improvement in any variable.\n The two self-paced exercise protocols were effective at improving neuromotor performance and functional capacity in the study sample and show promise as a safe, effective, cost-efficient, acceptable exercise model for primary and secondary prevention in the general population of community-dwelling older adults.", "This work analyses the short-term physiological and neurophysiological effects of a brisk walking programme in ageing, healthy, active men. Twenty-one men 63 to 72 years of age were recruited and separated into 2 groups. One group performed a walking programme (WP) (n = 11) and another served as control (C) group (n = 10). The walking programme lasted for twelve weeks and included five sessions per week. Several parameters were assessed before and after the programme for the WP group. The same tests were performed (separated by twelve weeks) in group C. During each assessment, the subjects were put through static and dynamic balance tests, spatio-temporal gait analysis, body composition measurements and determination of aerobic capacity and bone mineral density. The statistic analysis showed a significant improvement in dynamic balance performance, especially in lateral sway when the subjects kept their eyes open, an increase of VO(2) max and loss of fat mass in the WP group. However, no alterations appeared in spatiotemporal gait characteristics, static balance performance, lean mass or bone mineral density (total body and hip). According to these results, this walking programme may have positive effects on preventing ageing subjects from falling.", "To determine whether high-intensity functional training (FT) or strength training (ST) better enables impairment, disability, and functional gains among disabled community-dwelling elders.\n Randomized, blinded, prospective clinical trial in a large, tertiary care outpatient rehabilitation department. Fifteen elders (62-85 yrs old) referred for physical therapy with one or more impairments, including lower-limb arthritis, participated in 6 wks of FT (weekly outpatient and three to five times per week of home practice in rapid and correct execution of locomotor activities of daily living, including gait, stepping, and sit to stand) or progressive resistive ST using elastic bands with intensity, therapist contact, and home practice similar to those of FT.\n Both groups significantly improved their combined lower-extremity strength (hip abduction, ankle dorsiflexion, knee flexion, ankle plantarflexion, and knee extension) (P = 0.003), but no statistical difference between the ST and FT group gains (P = 0.203) was found. Subjects in both interventions improved their gait speed, but the FT group improved more than the ST group (P = 0.001). During chair rise, the FT group improved their maximum knee torque more than the ST group (P = 0.033), indicating that they employed a more controlled and efficient movement strategy.\n These data suggest that an intensive FT intervention results in strength improvements of comparable magnitude as those attained from ST and that FT also confers greater improvements in dynamic balance control and coordination while performing daily life tasks.", "The purpose of this study was to assess the effects of weight-bearing and non-weight-bearing exercise on strength, balance, gait and functional performance among older inpatients following hip fracture. Eighty people (mean age 81 years, SD 8) undergoing inpatient rehabilitation after fall-related hip fracture were randomised to receive two-week programs of either weight-bearing or non-weight-bearing exercise prescribed by a physiotherapist. Both groups improved markedly (in the order of 50%) on measures of physical ability. Overall there was little difference between groups in the extent of improvement, however post hoc testing identified some additional strength benefits for the non-weight-bearing group--non-affected leg hip flexion mean difference in extent of improvement was 9.3 N (95% CI 3.7 to 15.0), non-affected leg hip abduction mean difference in extent of improvement was 6.5 N (95% CI 0.1 to 12.9). There were also additional functional benefits for the weight-bearing group--improved ability to complete a lateral step-up on the affected leg with nil or one hand supports (OR 3.4, 95% CI 1.1 to 12.3) and the need for less supportive walking aids (p = 0.045). Weight-bearing and non-weight-bearing exercise programs produce similar effects on strength, balance, gait and functional performance among inpatients soon after hip fracture.", "Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance.\n Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 +/- 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension.\n At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed.\n In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further.", "Falls are common in elderly people. Possible consequences include serious injuries and the post-fall syndrome, with functional decline and limitation of physical activity. The present randomized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women. The subjects were individuals aged over 73 years, living at home in a western suburb of Tokyo, who had attended a comprehensive geriatric health check. Persons with a marked decline in the basic activities of daily living (ADL), hemiplegia, or those missing baseline data were excluded. Fifty-two subjects who expressed a wish to participate in the trial were randomized, 28 to an exercise-intervention group and 24 to a control group. Baseline data for age, handgrip force, walking speed, total serum cholesterol, serum albumin, basic ADL, visual and auditory impairments, self-rated health, and experience of falls did not differ significantly between the two groups. Beginning from June 2000, the intervention group attended a 6-month program of fall-prevention exercise classes aimed at improving leg strength, balance, and walking ability; this was supplemented by a home-based exercise program that focused on leg strength. The control group received only a pamphlet and advice on fall prevention. The average rate of attendance at exercise class was 75.3% (range, 64% to 86%). Participants showed significant improvements in tandem walk and functional reach after the intervention program, with enhanced self confidence. At the 8-month follow-up, the proportion of women with falls was 13.6% (3/22) in the intervention group and 40.9% (9/22) in the control group. At 20 months, the proportion remained unchanged, at 13.6% in the intervention group, but had increased to 54.5% (12/22) in the control group, which showed a statistically significant difference between the two groups (Fisher's exact test; P = 0.0097). The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group. We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term, contributing to improved health and quality of life in the elderly.\n Copyright 2004 Springer-Verlag", "The present study was conducted to determine the effect of 5-month exercise program on the prevention of falls in the elderly. The exercise training, which consisted of calisthenics, body balance training, muscle power training, and walking ability training 3 days/week improved the indices of the flexibility, body balance, muscle power, and walking ability and reduced the incidence of falls compared with non-exercise controls. The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.\n The present study was conducted to determine the effect of exercise on the prevention of falls in the elderly.\n Sixty-eight elderly ambulatory volunteers were randomly divided into two groups: the exercise and control groups. The daily exercise, which consisted of calisthenics, body balance training (tandem standing, tandem gait, and unipedal standing), muscle power training (chair-rising training), and walking ability training (stepping), were performed 3 days/week only in the exercise group. No exercise was performed in the control group.\n After the 5-month exercise program, the indices of the flexibility, body balance, muscle power, and walking ability significantly improved in the exercise group compared with the control group. The incidence of falls was significantly lower in the exercise group than in the control group (0.0% vs. 12.1%, P = 0.0363). The exercise program was safe and well tolerated in the elderly.\n The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.", "Sedentary behavior among older adults increases risk for chronic diseases. Physicians in a primary care setting can play an important role in promoting physical activity adoption among their older patients. The Physically Active for Life (PAL) project was a randomized, controlled trial comparing the efficacy of brief physician-delivered physical activity counseling to usual care on self-reported physical activity levels. The physical activity counseling was based on the Transtheoretical Model of Change and social learning theory. Twenty-four community-based primary care medical practices were recruited into the study; 12 were randomized to the Intervention condition and 12 to the Control condition. Physicians in the Intervention practices received training in the delivery of brief physical activity counseling. Subjects in the Intervention practices (n=181) received brief activity counseling matched to their stage of motivational readiness for physical activity, a patient manual, a follow-up appointment with their physician to discuss activity counseling, and newsletter mailings. Subjects in the Control practices (n=174) received standard care. Measures of motivational readiness for physical activity and the Physical Activity Scale for the Elderly (PASE) were administered to subjects in both conditions at baseline, 6 weeks following their initial appointment, and at 8 months. Results showed that at the 6-week follow-up, subjects in the Intervention condition were more likely to be in more advanced stages of motivational readiness for physical activity than subjects in the Control condition. This effect was not maintained at the 8 month follow-up and the intervention did not produce significant changes in PASE scores. Results suggest that more intensive, sustained interventions may be necessary to promote the adoption of physical activity among sedentary, middle-aged, and older adults in primary care medical practices.", "Using a randomized controlled trial, we tested the efficacy of a fall prevention intervention to reduce falls among adults in a community-based health promotion program. Adults aged 65 and older within two counties were recruited (control n = 257; intervention n = 286). After 12 months, there was a significant decrease in the number of falls in both groups (odds ratio = 0.45, p < .04), but the time by group membership interaction was not significant (χ(2) = 0.15, p < .69). Multivariate analysis did not find significant differences between the control and intervention groups for physical function as measured by a balance test or a sitting/standing test. Further research is needed on effective methods to deliver multifaceted fall interventions to older adults who are already being served by community health promotion programs.", "Age-related loss of foot-sole cutaneous sensation is very common and is associated with impaired balance control. This study investigated the effect of a balance-enhancing insole (designed to facilitate foot-sole sensation) on lateral gait stability and evaluated its effectiveness in daily life.\n Forty community-dwelling older adults (age 65-75) with moderate loss of foot-sole sensation (unrelated to neuropathy) were fitted with the same model of walking shoes. Half of the participants were assigned, at random, to wear the shoes with a facilitatory insole for 12 weeks; the other participants wore a conventional insole. A gait perturbation protocol, simulating uneven terrain, was performed at baseline and after wearing the assigned insoles for 12 weeks. Participants were tested with both types of insoles during each gait-testing session and sent in weekly postcards with information pertaining to insole comfort, hours of wear, and falls.\n The facilitatory insole improved lateral stability during gait, and this benefit did not habituate after 12 weeks of wearing the insole in daily life. Nine participants who wore conventional insoles experienced one or more falls, whereas only five of the facilitatory group fell. Although there were initial reports of mild discomfort in 10 cases, all but one participant tolerated the facilitatory insole, and most indicated that they would like to continue wearing the insole on a long-term basis.\n A relatively simple change in insole design can help to counter effects of age-related (non-neuropathic) decline in foot-sole sensitivity, and is a viable intervention to enhance balance control.", "To establish the effects of group exercise on mobility and strength.\n Randomized controlled trial.\n Two public hospital outpatient rehabilitation services.\n One hundred and seventy-three people (mean age 74.9 years, SD 10.8) with impaired mobility were randomized and 159 people (92%) completed the trial.\n Five-week, twice-weekly ;circuit-style' group exercise programme run by a physiotherapist (n = 85) and a no-intervention waiting list control group (n = 88).\n Three aspects of mobility: balance while standing and stepping (Step Test, semi-tandem and tandem stance times); sit-to-stand ability (rate and minimum height) and gait (6-metre and 6-minute walk tests). Lower limb muscle strength (knee flexion and extension).\n At retest, exercise participants had improved significantly more than their control counterparts on measures of balance while stepping, sit to stand and gait. Exercise participants averaged 1.6 more steps on the 15-second Step Test (95% confidence interval (CI) 0.5 to 2.8, P=0.005), walked an average of 0.12 m/s faster (95% CI 0.05 to 0.2, P=0.002) and took 2.5 fewer steps in 6 metres (95% CI -4.2 to -0.8, P=0.004). Exercise participants also averaged 0.04 more sit-to-stands/second, (95% CI 0.003 to 0.08, P=0.037) and walked an average of 30.9 metres further in 6 minutes (95% CI 9.4 to 52.4, P=0.005). There were no clinically important or statistically significant between-group differences at retest for the measures of strength (knee extension and flexion), balance while standing or minimal sit-to-stand height.\n This short-duration circuit class programme improved mobility, but not strength.", "The effects of weighted vest walking and strength-training exercises on bone mineral density (BMD), balance, strength, and self-efficacy were tested in older women. Eighteen women, age 69.2 +/- 3.5 years, were randomly assigned to an exercise group (EG) (n = 9), or a sedentary control group (CG) (n = 9). The EG participated in 32 weeks (three 1-h sessions/week) of supervised strength training and walking, stair climbing, and balance exercises while wearing weighted vests. The CG did not exercise. All women took Ca2+ and vitamin D during the study period. Measures included 1) BMD of the hip and lumbar spine measured by dual-energy X-ray absorptiometry, 2) strength, 3) balance, and 4) scores on a self-efficacy instrument. The EG had significant improvements in bone density of the femoral neck and balance and a significant weight loss (P < 0.05). There were no changes in self-efficacy in either group.", "Physical activity programs in nursing homes typically consist of seated, range of motion (ROM) exercises, regardless of resident abilities. The Functional Fitness for Long-Term Care (FFLTC) Program was designed not only to maintain ROM, but also to improve strength, balance, flexibility, mobility, and function. In addition, it was tailored to meet the needs of both high and low mobility residents.\n The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents (mean age 80) from five institutions. Persons were classified as low or high mobility and randomized into either the FFLTC program or a seated ROM program. Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes, three times per week. Assessments at baseline and 4 months consisted of mobility, balance, gait, flexibility, functional capacity, and several upper and lower extremity strength measures.\n Attendance averaged 86% for the FFLTC and 79% for the ROM classes. Four months of exercise led to significant improvements in mobility (16%), balance (9%), flexibility (36%), knee (55%), and hip (12%) strength for the FFLTC group. Shoulder strength was the only improvement found for the ROM group. The ROM group significantly deteriorated in some areas, particularly hip strength, mobility, and functional ability.\n Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.", "To evaluate the efficacy of a task-orientated intervention in enhancing competence in walking in people with stroke.\n Two-centre observer-blinded stratified block-randomized controlled trial.\n General community.\n Between May 2000 and February 2003, 91 individuals with a residual walking deficit within one year of a first or recurrent stroke consented to participate.\n The experimental intervention comprised 10 functional tasks designed to strengthen the lower extremities and enhance walking balance, speed and distance. The control intervention involved the practice of upper extremity activities. Subjects in both groups attended sessions three times a week for six weeks.\n Six-minute walk test (SMWT), 5-m walk (comfortable and maximum pace), Berg Balance Scale, timed 'up and go'.\n At baseline, subjects in the experimental (n = 44) and control (n = 47) groups walked an average distance of 209 m (SD = 126) and 204 m (SD =131), respectively, on the SMWT. Mean improvements of 40 m (SD =72), and 5 m (SD =66) were observed following the experimental and control interventions, respectively. The between-group difference was 35 m (95% confidence interval (CI) 7, 64). Significant between-group effects of 0.21 m/s (95% CI 0.12, 0.30) and of 0.11 m/s (95% CI 0.03, 0.19) in maximum and comfortable walking speed, respectively, were observed. People with a mild, moderate or severe walking deficit at baseline improved an average of 36 (SD =96), 55 (SD = 56) and 18 m (SD = 23), respectively, in SMWT performance following the experimental intervention.\n Study findings support the efficacy of a task-orientated intervention in enhancing walking distance and speed in the first year post stroke, particularly in people with moderate walking deficits.", "Home-based exercise is a viable solution for frail elderly individuals with difficulties in reaching exercise facilities outside home. The aim of this study was to determine the effects of a home-based video exercise program on physiological performance, functional capacity and health-related quality of life.\n Community-dwelling frail women > or = 75 yrs, receiving public home care, were randomized into a training group (n=30) and a control group (n=31). Participants exercised for 26 minutes, three times per week for five months. Both groups received a bi-weekly telephone call. The effect of intervention was evaluated by the physical performance test, mobility-tiredness score, maximal isometric handgrip and biceps strength, lower limb explosive power, repeated chair rise (5 times), 10-m maximal walking-speed, semi-tandem balance, and health-related quality of life, as measured by EQ-5D and self-rated health.\n Twenty-five participants (83%) in the training group and 28 (90%) in the control group completed the project. Adherence to the training protocol was on average 89.2%. At follow-up, between-group analysis revealed a significant difference only in EQ-5D (valued by time-trade-off tariffs), resulting from a significant decrease observed in the control group and a trend towards an increase in the training group (p=0.082). Significant within-group improvements, ranging from 8-35%, were also observed for the physical performance test, mobility-tiredness score, handgrip, biceps strength, chair rise, and 10-m maximal walking-speed in the training group, and for walking-speed and self-rated health in the control group.\n These results suggest that home-based training for frail older women using an exercise video induces lasting health-related quality-of-life (EQ- 5D). In addition, a tendency towards improvements in physiological performance and functional capacity was observed.", "To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women.\n A randomized, controlled trial of 12 months duration.\n Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia.\n One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community.\n Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength.\n Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program.\n These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.", "Physical exercise is expected to improve and maintain physical function in older people, thus promoting health and preventing or postponing the onset of disability in later life. The Sendai Silver Center Trial (SSCT) was a randomized controlled trial designed to evaluate the efficacy of exercise training among healthy free-living older people. Sixty-five eligible participants, aged from 60 to 81 years, were randomly allocated to an exercise group or a control group. The subjects in the exercise group were asked to attend training classes at the Sendai Silver Center, a municipal health and welfare facility in the center of Sendai City, at least twice a week for 25 weeks. Each training class, lasting two hours, started with a warm-up session, followed by an endurance session with a bicycle ergometer, and a resistance exercise training session using rubber films, and ended with a cool-down session. The subjects in the control group were asked to attend recreational classes at the Center twice a month. There were no drop-outs or accidents during the intervention. Comparison of maximum oxygen consumption (VO2max) before and after the 25-week intervention revealed a significant increase in the exercise group (2.1 ml/kg/min) but no significant change in the control group. Our result is equivalent to the participants becoming younger in aerobic capacity by five years after six months of exercise training.", "To compare the effects of three fall-prevention programs (education (ED), home safety assessment and modification (HSAM), and exercise training (ET)) on quality of life (QOL), functional balance and gait, activities of daily living (ADLs), fear of falling, and depression in adults aged 65 and older.\n A 4-month randomized trial.\n Randomized, controlled trial.\n One hundred fifty participants who had experienced a recent fall.\n QOL was assessed according to the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF), functional balance and gait according to functional reach and Tinetti balance and gait, ADLs according to the Older Americans Resources and Services questionnaire, fear of falling according to a visual analog scale, and depression level according to the Geriatric Depression Scale.\n The score changes for the ET group were 2.1 points greater on the physical domain (95% confidence interval (CI)=-1.2-5.3), 3.8 points greater on the psychological domain (95% CI=0.7-7.0), and for the WHOQOL-BREF, 3.4 points greater on the social domain (95% CI=0.7-6.1) and 3.2 points greater on the environmental domain (95% CI=0.6-5.7) than for the ED group. The score change for each domain of the WHOQOL-BREF for the HSAM group was greater than that for the ED group, although these results were not statistically significant. The ET group also had greater improvements in functional reach, Tinetti balance and gait, and fear of falling than the ED group.\n The QOL outcome supports the superiority of ET over the other two interventions in older people who have recently fallen. This finding also parallels those gathered from the functional measures.", "To determine whether a 12-month program of group exercise can improve physical functioning and reduce the rate of falling in frail older people.\n Cluster randomized, controlled trial of 12 months duration.\n Retirement villages in Sydney and Wollongong, Australia.\n Five hundred fifty-one people aged 62 to 95 (mean+/-standard deviation=79.5+/-6.4) who were living in self- and intermediate-care retirement villages.\n Accidental falls, choice stepping reaction time, 6-minute walk distance postural sway, leaning balance, simple reaction time, and lower-limb muscle strength.\n Two hundred eighty subjects were randomized to the weight-bearing group exercise (GE) intervention that was designed to improve the ability of subjects to undertake activities for daily living. Subjects randomized to the control arm (n=271) attended flexibility and relaxation (FR) classes (n=90) or did not participate in a group activity (n=181). In spite of the reduced precision of cluster randomization, there were few differences in the baseline characteristics of the GE and combined control (CC) subjects, although the mean age of the GE group was higher than that of the CC group, and there were fewer men in the GE group. The mean number of classes attended was 39.4+/-28.7 for the GE subjects and 31.5+/-25.2 for the FR subjects. After adjusting for age and sex, there were 22% fewer falls during the trial in the GE group than in the CC group (incident rate ratio=0.78, 95% confidence interval (CI)=0.62-0.99), and 31% fewer falls in the 173 subjects who had fallen in the past year (incident rate ratio=0.69, 95% CI=0.48-0.99). At 6-month retest, the GE group performed significantly better than the CC group in tests of choice stepping reaction time, 6-minute walking distance, and simple reaction time requiring a hand press. The groups did not differ at retest in tests of strength, sway, or leaning balance.\n These findings show that group exercise can prevent falls and maintain physical functioning in frail older people.", "The Getting Grounded Gracefully program, based on the Awareness Through Movement lessons of the Feldenkrais method, was designed to improve balance and function in older people. Fifty-five participants (mean age 75, 85% women) were randomized to an intervention (twice-weekly group classes over 8 wk) or a control group (continued with their usual activity) after being assessed at baseline and then reassessed 8 wk later. Significant improvement was identified for the intervention group relative to the control group using ANOVA between-groups repeated-measures analysis for the Modified Falls Efficacy Scale score (p = .003) and gait speed (p = .028), and a strong trend was evident in the timed up-and-go (p = .056). High class attendance (88%) and survey feedback indicate that the program was viewed positively by participants and might therefore be acceptable to other older people. Further investigation of the Getting Grounded Gracefully program is warranted.", "The aims of this randomised controlled trial were to determine if a high-intensity functional exercise program improves balance, gait ability, and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training. One hundred and ninety-one older persons dependent in activities of daily living, living in residential care facilities, and with a Mini-Mental State Examination (MMSE) score of ? 10 participated. They were randomised to a high-intensity functional exercise program or a control activity, which included 29 sessions over 3 months, as well as to protein-enriched energy supplement or placebo. Berg Balance Scale, self-paced and maximum gait speed, and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA, using the intention-to-treat principle. At three months, the exercise group had improved significantly in self-paced gait speed compared with the control group (mean difference 0.04 m/s, p = 0.02). At six months, there were significant improvements favouring the exercise group for Berg Balance Scale (1.9 points, p = 0.05), self-paced gait speed (0.05 m/s, p = 0.009), and lower-limb strength (10.8 kg, p = 0.03). No interaction effects were seen between the exercise and nutrition interventions. In conclusion, a high-intensity functional exercise program has positive long-term effects in balance, gait ability, and lower-limb strength for older persons dependent in activities of daily living. An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training.", "Intensive exercise training can lead to improvement in strength and functional performance in older people living at home and nursing home residents. There is little information whether intensive physical exercise may be applicable and effective in elderly patients suffering from the acute sequelae of injurious falls or hip surgery.\n To assess the feasibility, safety and efficacy of intensive, progressive physical training in rehabilitation after hip surgery.\n Prospective, randomised, placebo-controlled intervention study of a 3-months training intervention and a 3-months' follow-up.\n Physical training 6-8 weeks after hip surgery.\n Twenty-eight (15 intervention, 13 control) elderly patients with a history of injurious falls admitted to acute care or inpatient rehabilitation because of acute fall-related hip fracture or elective hip replacement.\n Progressive resistance and functional training to improve strength and functional performance.\n No training-related medical problems occurred in the study group. Twenty-four patients (86%) completed all assessments during the intervention and follow-up period. Adherence was excellent in both groups (intervention: 93, 0+/-13, 5% versus control: 96, 7+/-6, 2%). Training significantly increased strength, functional motor performance and balance and reduced fall-related behavioural and emotional problems. Some improvements in strength persisted during 3-months follow-up while other strength variables and functional performances were lost after cessation of training. Patients in the control group showed no change in strength, functional performance and emotional state during intervention and follow-up.\n Progressive resistance training and progressive functional training are safe and effective methods to increase strength and functional performance during rehabilitation in patients after hip surgery and a history of injurious falls. Because part of the training improvements were lost after stopping the training, a continuing training regime should be established.", "Falls in the elderly are a major health problem. Although exercise programs have been shown to reduce the risk of falls, the optimal exercise components, as well as the working mechanisms that underlie the effectiveness of these programs, have not yet been established.\n To test whether the Nijmegen Falls Prevention Program was effective in reducing falls and improving standing balance, balance confidence, and obstacle avoidance performance in community-dwelling elderly people.\n A total of 113 elderly with a history of falls participated in this study (exercise group, n = 79; control group, n = 28; dropouts before randomization, n = 6). Exercise sessions were held twice weekly for 5 weeks. Pre- and post-intervention fall monitoring and quantitative motor control assessments were performed. The outcome measures were the number of falls, standing balance and obstacle avoidance performance, and balance confidence scores.\n The number of falls in the exercise group decreased by 46% (incidence rate ratio (IRR) 0.54, 95% confidence interval (CI) 0.36-0.79) compared to the number of falls during the baseline period and by 46% (IRR 0.54, 95% CI 0.34-0.86) compared to the control group. Obstacle avoidance success rates improved significantly more in the exercise group (on average 12%) compared to the control group (on average 6%). Quiet stance and weight-shifting measures did not show significant effects of exercise. The exercise group also had a 6% increase of balance confidence scores.\n The Nijmegen Falls Prevention Program was effective in reducing the incidence of falls in otherwise healthy elderly. There was no evidence of improved control of posture as a mechanism underlying this result. In contrast, an obstacle avoidance task indicated that subjects improved their performance. Laboratory obstacle avoidance tests may therefore be better instruments to evaluate future fall prevention studies than posturographic balance assessments.\n Copyright (c) 2006 S. Karger AG, Basel.", "The aim of this randomized controlled trial was to evaluate the effect of a 3-month course of exercises on mobility, balance, disease-specific, and generic health-related quality of life (HRQOL) for women with osteoporosis and a history of vertebral fractures. Our results showed that exercises improved their mobility, balance, and HRQOL.\n The aim was to evaluate the effect of a 3-month course of circuit exercises plus a 3-h lesson on how to cope with osteoporosis on mobility, balance, and the HRQOL for postmenopausal women (60-84 years) with osteoporosis and a history of vertebral fracture. Our hypothesis was that a 3-month course would have a significantly positive effect on the women's mobility and balance as well as on their HRQOL.\n The participants (89) were randomized to an intervention group (IT) or a control group (CT) and assessed at baseline at 3 months and at 12 months with measurement of maximum walking speed (MWS), Timed Up and GO (TUG), Functional Reach (FR), the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis ('QUALEFFO-41') and the General Health Questionnaire (GHQ-20). The sample size was calculated with reference to walking speed (primary outcome), and the statistical approaches used were Student's t test or the chi-square test.\n At 3 months, better results were registered on the primary outcome, MWS as well as TUG, FR, sum score of GHQ-20, and \"QUALEFFO-41: mental function\" in the IT compared with the CT. At 12 months, those in the IT had a better result on the primary outcome, MWS as well as TUG, \"QUALEFFO-41: total score\" \"QUALEFFO-41: mental function\", \"QUALEFFO-41: physical function\", and \"QULEFFO-41: pain\" compared with CT.\n Circuit exercises will improve mobility and health-related quality of life of elderly women with osteoporosis and a history of vertebral fractures.", "To evaluate the additional effect of functional exercises on balance and lower extremity function among hostel-dwelling elderly people partaking in strength,training.\n A randomized two-group parallel controlled trial.\n A senior resident's hostel in Switzerland.\n Thirty-two individuals randomized to either strength or strength and functional exercise groups.\n Both groups received machine-driven strength training for 45 min, twice weekly, for 12 weeks. The strength and functional exercises group received an additional 30 min of functional exercise training, once weekly.\n Tinetti test, balance tests and a physical performance test. Assessments were performed before and after the intervention.\n Improvements for the balance test depended on the type of training (significant interaction effects [F(1,20)= 6.7; P = 0.018]). This test improved from 11.3 +/- 11.7 to 17 +/- 11.2 (P = 0.009) in the combined training group (n = 12) and remained from 7.3 +/- 9.5 to 6.9 +/- 9.2 unchanged (P = 0.821) in the strength training group (n = 13). A significant difference between groups following training was observed (P = 0.031). The Tinetti balance score and the chair stand test of the physical performance assessment improved from 14.3 +/- 1.9 to 15.3 +/- 1.1 (P = 0.026) and 1.8 +/- 1.2 to 2.8 +/- 1.1 (P = 0.012) respectively in the combined training group only.\n Our findings suggest that twice-weekly lower extremity strength training of 12 weeks' duration in hostel-dwelling elderly people only improves task-specific balance performance and lower extremity physical function when additional functional exercises are added.", "To use a pilot study to compare two physiotherapy approaches to improve walking in patients with gait disturbance due to multiple sclerosis (MS).\n Patients were assessed and then randomly assigned to one of two groups using a block randomization technique. They were treated by the research physiotherapist for a minimum of 15 treatments over a 5-7-week period and then reassessed by an independent therapist one week after treatment.\n Both assessment and treatment were undertaken at a specialist rehabilitation centre.\n Outpatients with clinically stable MS (chronic progressive or relapsing-remitting types) who were referred for physiotherapy to improve their mobility.\n Comparison was between a facilitation (impairment-based) approach and a task-oriented (disability-focused) approach.\n Mobility was assessed using four measures: the 10-metre timed walk, the Rivermead Mobility Index, stride length and the Rivermead Visual Gait Assessment. Balance was assessed using the Berg Balance Test.\n Twenty-three patients were entered, and 10 in each group completed the study. The groups were similar on all measured items both before and after treatment. There was no significant difference in improvement between the two approaches. Following treatment, patients in both groups showed a significant overall improvement (p < 0.05) in both impairment and disability measures.\n No significant differences in effectiveness between the two methods were demonstrated. Both a task-oriented approach and a facilitation approach to the treatment of MS outpatients were associated with improved mobility.", "This randomized controlled trial was designed to investigate the effect of a 6-month home-based exercise program versus control (usual activities) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture. Twelve-month assessments of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained. The home exercise program followed a \"lifestyle exercise\" approach where participants completed exercises 60 min per day, 3 days a week and could complete exercises in small periods of time throughout the day. Exercise activities included stretching, strength training and aerobics (i.e. walking). Participants were assessed at baseline, 6 months, and 12 months using the Osteoporosis Quality of Life Questionnaire (OQLQ), the Sickness Impact Profile (SIP), a balance test, and the Timed Up And Go test. Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck. Quality of life (OQLQ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms (P=0.003), emotion (P=0.01) and leisure (P=0.03). Results from the balance test indicated a greater effect in the exercise group over 12 months (P<0.05). There were no significant differences between groups in measures of Timed Up and Go, SIP at 6 and 12 months, and femoral neck and lumbar spine bone mineral density at 12 months. Home-based exercise with minimal supervision improves quality of life in elderly women with vertebral fractures. Future research is needed to determine if home exercise programs reduce falls and fall-related injuries in the elderly.", "Forty-eight community living women 66-87 years old volunteered to participate in a 12-month prospective, randomized, controlled, trial. The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function. The participants were pairwise age-matched and randomly assigned to either an exercise group (n=24) or a control group (n=24). Twenty-one subjects in the intervention group and 19 in the control group completed the study. The exercise program lasted for 50 min and consisted of a combination of strengthening, aerobic, balance and coordination exercises. The mean percentage of scheduled sessions attended for the exercise group was 67%. At the completion of the study, the intervention group showed significant increments in bone mineral density of the Ward's triangle (8.4%, P<0.01) as well as improvement in maximum walking speed (11.4%, P<0.001) and isometric grip strength (9.9%, P<0.05), as compared to the control group. The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability. This program could be suitable for older community living women in general, and might, therefore, have important implications for fracture prevention.", "To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance.\n Randomized clinical trial.\n University hospital physiotherapy department.\n Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score (SD) of -1.8 (0.8).\n A three-month programme consisting of exercise/protein including training of muscular strength, co-ordination, balance and endurance. Calcium/ vitamin D was supplemented in all participants for a 12-month period.\n Assessment took place prior to and following the months 3, 6, 9 and at the end of the study; primary dependent variables assessed were risk of falling (Berg Balance Test) and postural balance (forceplate). Secondary measures included body composition, strength, activity level, number of falls, bone mineral content, biochemical indices, nutritional status and general health.\n Significant reductions of risk of falling (repeated measures ANOVA F = 8.90, P = 0.008), an increase in muscular strength (ANOVA F = 3.0, P = 0.03), and an increase in activity level (ANOVA F = 3.38, P = 0.02) were found in the experimental group as compared to the control group. Further on, there was 89% reduction of falls reported in the experimental group (experimental pre/post 8/1 falls; control group pre/post 5/6 falls).\n This study provides support for our intervention programme aimed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis. The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger randomized trial.", "To investigate the effect of an additional vestibular stimulated exercise programme on balance for patients with benign paroxysmal positional vertigo.\n Randomized controlled trial.\n Medical centre.\n Twenty-six subjects with benign paroxysmal positional vertigo involving the unilateral posterior semicircular canal.\n Subjects were randomized into experimental or control groups. Thirteen subjects in the experimental group received the canalith repositioning manoeuvre and vestibular stimulated exercise training three times a week for four weeks. Thirteen subjects in the control group received only the canalith repositioning manoeuvre.\n Static balance tests, tandem walk test, Dynamic Gait Index and subjective rating of the intensity of vertigo were measured at baseline, two-week and four-week assessments.\n Compared with the control group, subjects in the experimental group demonstrated a statistically significant improvement in single leg stance with eyes closed at the two-week assessment (P<0.05). Furthermore, stance on foam surface with eyes closed, single-leg stance with eyes closed, and Dynamic Gait Index at the four-week assessment were also significantly improved (P<0.05).\n The present study demonstrated that additional exercise training, which emphasizes vestibular stimulation, can improve balance ability and functional gait performance among patients with benign paroxysmal positional vertigo who had already undergone the canalith repositioning manoeuvre.", "Mudge S, Barber PA, Stott NS. Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial.\n To determine whether circuit-based rehabilitation would increase the amount and rate that individuals with stroke walk in their usual environments.\n Single-blind randomized controlled trial.\n Rehabilitation clinic.\n Sixty participants with a residual gait deficit at least 6 months after stroke originally enrolled in the study. Two withdrew in the initial phase, leaving 58 participants (median age, 71.5y; range, 39.0-89.0y) who were randomized to the 2 intervention groups.\n The exercise group had 12 sessions of clinic-based rehabilitation delivered in a circuit class designed to improve walking. The control group received a comparable duration of group social and educational classes.\n Usual walking performance was assessed using the StepWatch Activity Monitor. Clinical tests were gait speed (timed 10-meter walk) and endurance (six-minute walk test [6MWT]), confidence (Activities-Based Confidence Scale), self-reported mobility (Rivermead Mobility Index [RMI]), and self-reported physical activity (Physical Activity and Disability Scale).\n Intention-to-treat analysis revealed that the exercise group showed a significantly greater distance for the 6MWT than the control group immediately after the intervention (P=.030) but that this effect was not retained 3 months later. There were no changes in the StepWatch measures of usual walking performance for either group. The exercise and control groups had significantly different gait speed (P=.038) and scores on the RMI (P=.025) at the 3-month follow-up. These differences represented a greater decline in the control group compared with the exercise group for both outcome measures.\n Circuit-based rehabilitation leads to improvements in gait endurance but does not change the amount or rate of walking performance in usual environments. Clinical gains made by the exercise group were lost 3 months later. Future studies should consider whether rehabilitation needs to occur in usual environments to improve walking performance.", "The present study has been carried out to investigate the effects of group-based Turkish folkloric dances on physical performance, balance, depression and quality of life (QoL) in 40 healthy adult elderly females over the age of 65 years. Subjects were randomly allocated into Group 1 (folkloric dance-based exercise) and Group 2 (control). A 8-week dance-based exercise program was performed. Outcome measures included a 20-m walk test, a 6-min walk test, stair climbing and chair rise time, Berg balance scale (BBS), the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36), and geriatric depression scale (GDS) questionnaires. In Group 1 statistically significant improvements were found in most of the physical performance tests, BBS and some SF-36 subscales after the exercise (p<0.05). In the Group 2 there was no clinically significant change in the variables. Comparing the groups, significant improvements in favor of Group 1 have emerged in most of the functional performance tests, in some of the SF-36 subscales and BBS score (p<0.05). We achieved improvements in physical performance, balance and QoL in elderly females. Application of folkloric dance specific to countries as an exercise program for elderly people may be helpful.", "To investigate the effects of whole body vibration in the elderly.\n Randomized controlled trial.\n Nursing home.\n Forty-two elderly volunteers.\n Six-week vibration intervention plus physical therapy (PT) (n=22) or PT alone (n=20).\n We assessed gait and body balance using the Tinetti test (maximum scores of 12 for gait, 16 for body balance, 28 for global score), motor capacity using the Timed Up & Go (TUG) test, and health-related quality of life (HRQOL) using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).\n After 6 weeks, the vibration intervention group improved by a mean +/- standard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P <.001). The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P <.001). TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P <.001). The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group.\n Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients.", "After stroke, persistent gait deficits cause debilitating falls and poor functional mobility. Gait restoration can preclude these outcomes. Sixteen subjects (>12 months poststroke) were randomized to two gait training groups. Group 1 received 12 weeks of treatment, 4 times a week, 90 min per session, including 30 min strengthening and coordination, 30 min over-ground gait training, and 30 min weight-supported treadmill training. Group 2 received the same treatment, but also used functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM) for each aspect of treatment. Outcome measures were kinematics of gait swing phase. Both groups showed no significant pre-/posttreatment gains in peak swing hip flexion. Group 1 (no FNS) had no significant gains in other gait components at posttreatment or at follow-up. Group 2 (FNS-IM) had significant gains in peak swing knee flexion and mid-swing ankle dorsiflexion (p < 0.05) that were maintained for 6 months." ]

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[ "The relationship between tobacco access and use among adolescents: a four community study.", "The effects of community policies to reduce youth access to tobacco.", "Interventions with retailers to reduce cigarette sales to minors: a randomised controlled trial.", "The effect of enforcing tobacco-sales laws on adolescents' access to tobacco and smoking behavior.", "Is restricting tobacco sales the answer to adolescent smoking?", "Reducing underage cigarette sales in an isolated community: the effect on adolescent cigarette supplies.", "Evaluation of an enforcement program to reduce tobacco sales to minors.", "The effects of licensing and inspection enforcement to reduce tobacco sales to minors in Greater Philadelphia, 1994-1998.", "Mass media interventions to reduce youth smoking prevalence.", "The impact on tobacco use of branded youth anti-tobacco activities and family communications about tobacco.", "The effects of combining education and enforcement to reduce tobacco sales to minors. A study of four northern California communities.", "Population tobacco control interventions and their effects on social inequalities in smoking: placing an equity lens on existing systematic reviews.", "Active enforcement of cigarette control laws in the prevention of cigarette sales to minors.", "A longitudinal study of exposure to retail cigarette advertising and smoking initiation.", "Effects of an advocacy intervention to reduce smoking among teenagers.", "A randomised controlled trial of a community intervention to prevent adolescent tobacco use.", "Tobacco marketing and adolescent smoking: more support for a causal inference.", "Using the internet to assist smoking prevention and cessation in schools: a randomized, controlled trial.", "Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.", "Changes among retailers selling cigarettes to minors.", "Teen reach: outcomes from a randomized, controlled trial of a tobacco reduction program for teens seen in primary medical care.", "The impact of behavioural interventions on young people's attitudes toward tobacco use.", "Smokeless tobacco cessation cluster randomized trial with rural high school males: intervention interaction with baseline smoking.", "Preventing tobacco use among young people in India: Project MYTRI." ]

[ "The objective of this study was to examine the effectiveness of a longitudinal community intervention on the reduction of tobacco sales to minors and subsequent effects on tobacco consumption by youths. The study was conducted in Monterey County, CA. Four rural communities were randomized into treatment and comparison arms of the study and middle and high school students in each of these communities completed surveys assessing knowledge, attitude, and behavior. The main outcome measures were retail tobacco sales to minors as measured through store visits (tobacco purchase surveys) and self-reported consumption of tobacco. Over a three-year period, a diverse array of community interventions were implemented in the intervention communities. These included community education, merchant education, and voluntary policy change. In the treatment communities, the proportion of stores selling tobacco to minors dropped from 75% at baseline to 0% at the final post-test. In the comparison communities, the proportions were 64% and 39%, respectively. Although the availability of tobacco through commercial outlets was reduced substantially in intervention communities, youths reported still being able to obtain tobacco from other sources. Predicted treatment effects on reported use of tobacco among youths were observed cross-sectionally and longitudinally for younger students (7th graders). The intervention did not impact tobacco use among older students (9th and 11th graders) although the trends were in the predicted direction for 9th graders. A significant intervention effect was found for sex--females in the intervention communities were less likely to use tobacco post-intervention than females in the comparison communities. Tobacco sales to minors can be reduced through a broad-based intervention. To prevent or reduce tobacco use by youths, however, multiple supply-and demand-focused strategies are needed.", "This study tested the hypothesis that adoption and implementation of local policies regarding youth access to tobacco can affect adolescent smoking.\n A randomized community trial was conducted in 14 Minnesota communities. Seven intervention communities participated in a 32-month community-organizing effort to mobilize citizens and activate the community. The goal was to change ordinances, merchant policies and practices, and enforcement practices to reduce youth access to tobacco. Outcome measures were derived from surveys of students before and after the intervention and from tobacco purchase attempts in all retail outlets in the communities. Data analyses used mixed-model regression to account for the clustering within communities and to adjust for covariates.\n Each intervention community passed a comprehensive youth access ordinance. Intervention communities showed less pronounced increases in adolescent daily smoking relative to control communities. Tobacco purchase success declined somewhat more in intervention than control communities during the study period, but this difference was not statistically significant.\n This study provides compelling evidence that policies designed to reduce youth access to tobacco can have a significant effect on adolescent smoking rates.", "We aimed to determine the relative effectiveness of an education intervention and a threat-of-enforcement intervention in reducing sales of cigarettes to under-age youth by randomly allocating 300 retailers in a nonmetropolitan region of New South Wales to: a control group with no intervention; a minimal-intervention group, which received an educational letter; and a maximal-intervention group, which received a threat of enforcement followed by a visit from a public health officer. Retailers were checked for compliance at pretest and post-test, six months apart, by twelve 18-year-olds who were judged by independent raters to look younger. The retailers were surveyed by telephone at both times for knowledge, attitudes and self-reported sales practices. Neither intervention achieved significant improvements for the two key behavioural outcomes: requiring proof of age and display of a warning sign. Neither was there an intervention effect on knowledge about the law. The greatest improvement in the proportion of retailers who believed that the legal age should be 18 or over was in the minimal-intervention group, and both intervention groups were less likely than the control group at post-test to think that it was acceptable to sell to a person who was nearly 18. There was poor overall compliance with the revised legislation at pre-test. The finding of a pretest-to-post-test improvement but no differential intervention effect highlights the methodological difficulties of such research. The interventions may, however, have been partly successful in modifying the attitudes of retailers.", "Enforcing laws banning tobacco sales to minors is widely advocated as a way to reduce young people's access to tobacco and tobacco use. Whether this approach is successful is not known.\n In a two-year controlled study, we assessed sales of tobacco to minors and young people's access to and use of tobacco in six Massachusetts communities. Three communities (the intervention group) enforced tobacco-sales laws, whereas three matched communities (the control group) did not. To assess compliance with the law, minors working for the study investigators attempted to purchase tobacco from all retail vendors in each community every six months. Three annual anonymous surveys of a total of 22,021 students in grades 9 through 12 (response rate, 84 percent) measured access to tobacco and smoking behavior.\n At base line, 68 percent of 487 vendors sold tobacco to minors. Compliance with the law improved significantly faster in the intervention communities than in the controls (P<0.001). By the study's end, 82 percent of the merchants in the intervention communities complied with the law, as compared with 45 percent in the control communities (P<0.001). However, adolescents under 18 years old reported only a small drop in their ability to purchase tobacco and no decline in its use. Communities with and those without enforcement programs did not differ with respect to these outcomes.\n Enforcing tobacco-sales laws improved merchants' compliance and reduced illegal sales to minors but did not alter adolescents' perceived access to tobacco or their smoking. Test purchases of tobacco do not accurately reflect adolescents' self-reported access to tobacco, and reducing illegal sales to less than 20 percent of attempts -- the goal of a new federal law-- may not decrease young people's access to or use of tobacco.", "Enforcement of legislation restricting retail access to tobacco is increasingly relied on to reduce adolescent smoking rates. In 1996, health authorities in the Northern Sydney Health Area began monitoring tobacco retailer compliance (PROOF program) with staged purchase attempts by adolescents below the legal age (18 years). Repeat cross-sectional surveys before (1995) and after (2000) the introduction of PROOF monitored changes in adolescent smoking behaviour. Students aged 12 to 17 years from 11 Northern Sydney metropolitan public secondary schools were surveyed for self-reported smoking and tobacco purchasing behavior in 1995 (n = 5,206) and 2000 (n = 4,120). Between 1996 and 2000, 545 retailer compliance checks found 34% unlawfully sold cigarettes to minors and 28% of these repeated the offence. Nine prosecutions resulted. Modelling revealed a significant association between the intervention and never having smoked (adjusted OR = 1.16, 95% CI = 1.01-1.33) although there was no significant association with being a current smoker. The odds of being a smoker were greater for students from coeducational schools, with this effect being modified by gender. There was no reduction in adolescent smoking with active enforcement of tobacco access laws despite an apparent increase in students who reported never to have smoked.", "The current study explored the practicality of preventing underage retail cigarette sales and the relationship to cigarette supplies among adolescents.\n In Fort Morgan, Colorado, an isolated rural community with below-average socioeconomic status and a large Latino population, supervised teenaged employees repeatedly attempted to buy cigarettes from every store over a 9-month period in 2005. Repeated violations were penalized. Cigarette acquisition and exchange among community adolescents were assessed before and after intervention using a high school student survey.\n The measured violation rate declined from 47% in the first week to 3.4% during the final three months, and high school student reliance on retail cigarette purchases declined. Adolescent cigarette supplies declined by approximately 15%.\n Isolated rural communities can reduce adolescent cigarette supplies by conducting consistent enforcement against retail cigarette sales to minors. Previous research suggests that reducing these sales may help reduce adolescent smoking. The current study demonstrates that enforcement is practical and effective.", "This study evaluated an active enforcement program to increase retailers' compliance with the law prohibiting tobacco sales to minors.\n Tobacco sales to minors were monitored in 319 outlets in 6 pairs of communities in Erie County, New York. One community in each pair was randomly assigned to an enforcement intervention.\n Retailers' compliance with the law increased from 35% in 1994 to 73% in 1995. However, the change in compliance rates was roughly the same for stores in the enforcement and nonenforcement communities.\n Active compliance checking of retail outlets as a strategy to reduce illegal tobacco sales to minors may only be necessary insofar as it contributes to an increase in retailers' perception that the threat of enforcement is real.", "This study examined the changes in tobacco sales to minors after active enforcement of merchant compliance to the Synar regulation and the city of Philadelphia Youth Access to Tobacco Ordinance 732. Data for the present study were obtained through Tobacco-free Education and Action Coalition for Health (TEACH) Program in a 5-year, follow-up retail compliance check survey of 1649 stores in 14 cluster areas of Philadelphia, PA. Trend analysis was conducted ofthe sales of tobacco to minors by type of retail outlet, gender, and age of the buyer, and gender, age, and race of the store clerk, and whether restriction policy signs were posted. Analysis indicates that there was a reduction in tobacco sales to minors after implementation of enforcement; sales dropped from 85% in 1994 to 43% in 1998. There were less sales to minors when signs were posted. There were differences in sales if the buyer was asked his or her age and whether the minor was asked to show identification. In addition, the age of the buyer and the brand of cigarettes were associated with sales. Future research should focus on both commercial and social availability and provision of tobacco to minors.", "Mass media interventions for reduction of youth cigarette smoking have been recommended based on a broad array of evidence, although few randomized community trials have been reported.\n Four matched pairs of independent media markets were identified; one member of each pair was randomized to receive the intervention. School surveys were conducted in all markets, in 2001 before (n=19,966) and in 2005 after (n=23,246) the interventions were completed.\n Grade 7-12 students from public schools in these eight medium-sized metropolitan areas participated in the summative evaluations; Grades 4-12 students were targeted to receive mass media interventions in four of these markets.\n Four simultaneous campaigns consisting of specially developed messages based on behavioral theory and targeted to defined age groups of racially and ethnically diverse young people were placed in popular TV, cable, and radio programming using purchased time for 4 years.\n Prevalence of youth smoking and psychosocial mediators of smoking.\n No significant impacts of these interventions on smoking behaviors or mediators were found for the overall samples. A positive effect was found for one mediator in subgroups. Among Hispanic participants a marginally favorable effect on smoking prevalence and significant effects on mediators were found. General awareness of smoking prevention TV messages was slightly higher over time in the intervention areas.\n Mass media interventions alone were unable to induce an incremental difference in youth smoking prevalence, probably because of a relatively strong tobacco control environment that included a substantial national smoking prevention media campaign.\n Copyright 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.", "In a randomized controlled trial, we evaluated the effect on tobacco use onset among middle school students of Family Communications (FC) activities designed to mobilize parental influences against tobacco use and Youth Anti-tobacco Activities (YAT) designed to market anti-tobacco norms to adolescents. We conducted a simple, two-condition experimental design in which 40 middle schools, with a prevalence of tobacco use at or above the Oregon median, received, by random assignment, either the intervention or no intervention. State, county, and local prevention coordinators around Oregon served as liaisons to schools. To generate interest, staff made presentations to these groups and distributed marketing packets at several conferences. Dependent variables were indices of smoking prevalence and use of smokeless tobacco (ST) in the prior month. Additionally, we created an intervention manual so that other communities could replicate this study. The findings suggest that efforts to influence parents to discourage their children's tobacco use and efforts to market an anti-tobacco perspective to teens are effective in preventing smoking. The impact of YAT is consistent with experimental and nonexperimental evaluations of media campaigns to influence young people not to smoke.", "To examine the effects of a community education and law enforcement intervention on illegal tobacco sales to minors.\n A 2-year, before and after trial with retail stores as the unit of analysis.\n Implementation occurred in four suburban California communities with populations of 25,000 to 100,000.\n All the retail stores in one intervention community and half the retail stores, randomly selected, in the other three intervention communities (n = 169) were visited by minors aged 14 to 16 years with the intent to purchase tobacco.\n Ongoing community and merchant education and four law enforcement operations were conducted.\n Over-the-counter and vending machine sales of tobacco to minors were the primary outcomes.\n Among a cohort of stores visited by minors at the pretest (n = 104) in June 1988, 71% sold tobacco over the counter and 92% sold tobacco through vending machines. At posttest 2 in May 1990, 24% sold tobacco over the counter and 93% sold tobacco through vending machines. Of the 31 stores issued citations, 16 were followed into the courts where the fines were dismissed or reduced.\n Education alone had a limited effect on reducing illegal tobacco sales to minors. It did promote community support for more aggressive enforcement strategies. Education plus enforcement decreased significantly over-the-counter sales; vending machine sales were unaffected by these interventions. The lack of support at the judicial level may temper the effectiveness of enforcement. Legislative remedies addressing judicial obstacles and vending machine sales are needed.", "With smoking increasingly confined to lower socio-economic groups, the tobacco control community has been urged to identify which population-level tobacco control interventions work in order to help tackle smoking-related health inequalities. Systematic reviews have a crucial role to play in this task. This overview was therefore carried out in order to (i) summarise the evidence from existing systematic reviews of population-level tobacco control interventions, and (ii) assess the need for a new systematic review of primary studies, with the aim of assessing the differential effects of such interventions.\n Systematic review methods were used to evaluate existing systematic reviews that assessed a population-level tobacco control intervention and which reported characteristics of included participants in terms of at least one socio-demographic or socio-economic factor.\n Nineteen systematic reviews were included. Four reviews assessed interventions aimed at the population level alone, whilst fifteen included at least one primary study that examined this type of intervention. Four reviews assessed youth access restrictions, one assessed the effects of increasing the unit price of tobacco, and six assessed smoking bans or restrictions. Of the eight remaining reviews, six assessed multi-component community based interventions, in which the population-level interventions were part of a wider tobacco control programme, and two assessed the impact of smoking bans or restrictions in reducing exposure to environmental tobacco smoke. We found tentative evidence that the effect of increasing the unit price of tobacco products may vary between ethnic and socio-economic groups, and between males and females. However, differences in the context and the results of different reviews made it difficult to draw any firm conclusions. Few identified reviews explicitly attempted to examine differences in intervention effects between socio-demographic groups. Therefore on the basis of these reviews the potential for smoking bans, and youth access restrictions to decrease social inequalities in smoking remains unknown.\n There is preliminary evidence that increases in the unit price of tobacco may have the potential to reduce smoking related health inequalities. There is a need for equity effects to be explicitly evaluated in future systematic reviews and in primary research assessing the effects of population tobacco control interventions.", "To assess the effect that cigarette legislation would have on reducing merchant sales rates of cigarettes to minors and the affect on adolescent smoking behavior.\n Observational survey of merchant selling behaviors and adolescent smoking habits before and after passage of legislation.\n The setting for the merchant survey was Woodridge, Ill (population 25,200), a suburban community of Chicago. The surveys were distributed to adolescents in the local junior high school.\n Convenience sample of both merchants and adolescent students.\n Passage of community antismoking legislation.\n Percentage of stores selling cigarettes to minors in Woodridge and percentage of students who had experimented with cigarettes or were regular smokers.\n Merchant sales rates in Woodridge decreased from a baseline of 70% before legislation to less than 5% in 1.5 years of compliance checking after legislation. Student surveys showed that the rates of cigarette experimentation and regular use of cigarettes by adolescents were reduced by over 50%.\n Cigarette control laws can be effective in significantly reducing the rate of cigarettes sold by merchants and rates of cigarette use by adolescents. Key elements of successful legislation implementation are consistent compliance checking and heightened community awareness of the problems and prevalence of adolescent smoking.", "Accumulating evidence suggests that widespread advertising for cigarettes at the point of sale encourages adolescents to smoke; however, no longitudinal study of exposure to retail tobacco advertising and smoking behavior has been reported.\n A school-based survey included 1681 adolescents (aged 11-14 years) who had never smoked. One measure of exposure assessed the frequency of visiting types of stores that contain the most cigarette advertising. A more detailed measure combined data about visiting stores near school with observations of cigarette advertisements and pack displays in those stores. Follow-up surveys 12 and 30 months after baseline (retention rate: 81%) documented the transition from never to ever smoking, even just a puff.\n After 12 months, 18% of adolescents initiated smoking, but the incidence was 29% among students who visited convenience, liquor, or small grocery stores at least twice per week and 9% among those who reported the lowest visit frequency (less than twice per month). Adjusting for multiple risk factors, the odds of initiation remained significantly higher (odds ratio: 1.64 [95% confidence interval: 1.06-2.55]) for adolescents who reported moderate visit frequency (0.5-1.9 visits per week), and the odds of initiation more than doubled for those who visited > or = 2 times per week (odds ratio: 2.58 [95% confidence interval: 1.68-3.97]). Similar associations were observed for the more detailed exposure measure and persisted at 30 months.\n Exposure to retail cigarette advertising is a risk factor for smoking initiation. Policies and parenting practices that limit adolescents' exposure to retail cigarette advertising could improve smoking prevention efforts.", "To test whether high school students' participation in advocacy activities related to the advertising, availability, and use of tobacco in their communities would prevent or reduce their own tobacco use.\n Ten continuation high schools in northern California, randomly assigned to a semester-long program in which students either carried out advocacy activities to counter environmental-level smoking influences in their communities (treatment) or learned about drug and alcohol abuse prevention (control).\n Eleventh and 12th grade high school students; 5 (advocacy) treatment and 5 control schools over 4 semesters from 2000 through 2002.\n Self-reported smoking defined as nonsmokers (those who had never smoked tobacco or those who were former smokers), light smokers (those who smoked <1 pack per week), or regular smokers (those who smoked >or=1 pack per week), and confirmed by carbon monoxide level readings. The following 3 constructs related to social cognitive theory- perceived incentive value, perceived self-efficacy, and outcome expectancies-were assessed.\n There was a significant net change from baseline to the end of the semester (after the intervention) between treatment and control schools for students who were regular smokers, but not for students who were nonsmokers or light smokers. Regular smoking decreased 3.8% in treatment schools and increased 1.5% in control schools (P<.001). Regular smoking continued to decrease at 6 months after the intervention in treatment schools, with a total change in prevalence from 25.1% to 20.3%. Involvement in community-advocacy activities and the 3 social constructs-perceived incentive value, perceived self-efficacy, and outcome expectancies-also showed significant net changes between treatment and control schools (all P values <.01).\n Student engagement in community-advocacy activities that addressed environmental influences of cigarette smoking resulted in significant decreases in regular smoking.", "Experimental evaluation of comprehensive community wide programme to prevent adolescent tobacco use.\n Eight pairs of small Oregon communities (population 1700 to 13 500) were randomly assigned to receive a school based prevention programme or the school based programme plus a community programme. Effects were assessed through five annual surveys (time 1-5) of seventh and ninth grade (ages 12-15 years) students.\n The community programme included: (a) media advocacy, (b) youth anti-tobacco activities, (c) family communications about tobacco use, and (d) reduction of youth access to tobacco.\n The prevalence of self reported smoking and smokeless tobacco use in the week before assessment.\n The community programme had significant effects on the prevalence of weekly cigarette use at times 2 and 5 and the effect approached significance at time 4. An effect on the slope of prevalence across time points was evident only when time 2 data points were eliminated from the analysis. The intervention affected the prevalence of smokeless tobacco among grade 9 boys at time 2. There were also significant effects on the slope of alcohol use among ninth graders and the quadratic slope of marijuana for all students.\n The results suggest that comprehensive community wide interventions can improve on the preventive effect of school based tobacco prevention programmes and that effective tobacco prevention may prevent other substance use.", "This prospective study examined the effect of tobacco marketing on progression to established smoking.\n Massachusetts adolescents (n = 529) who at baseline had smoked no more than 1 cigarette were reinterviewed by telephone in 1997. Analyses examined the effect of receptivity to tobacco marketing at baseline on progression to established smoking, controlling for significant covariates.\n Adolescents who, at baseline, owned a tobacco promotional item and named a brand whose advertisements attracted their attention were more than twice as likely to become established smokers (odds ratio = 2.70) than adolescents who did neither.\n Participation in tobacco marketing often precedes, and is likely to facilitate, progression to established smoking. Hence, restrictions on tobacco marketing and promotion could reduce addiction to tobacco.", "To evaluate the impact of a classroom-based, Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents.\n A two-group randomized control trial with 1,402 male and female students in grades 9 through 11 from 14 secondary schools in Toronto, Canada. Participants were randomly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up. The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine (http://www.smokingzine.org) integrated into a program that included a paper-based journal, a small group form of motivational interviewing, and tailored e-mails.\n Resistance to smoking, behavioral intentions to smoke, and cigarette use were assessed at baseline, postintervention, and three- and six-month follow-up. Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time.\n The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months. The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period.\n The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months. By providing an accessible and attractive method of engaging young people in smoking prevention and cessation, this interactive and integrated program provides a novel vehicle for school- and population-level health promotion.", "The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.", "This study analyzes changes over a three-year period among Ontario retailers selling cigarettes to minors. Under supervision, 13 and 14-year-old minors were sent into stores to attempt to buy cigarettes. These minor-purchase-events (MPEs) were carried out in a local health unit that had implemented a community-based intervention and in an adjoining comparison health unit. After the local program we observed a large reduction (from 46% to 6%) in merchants willing to sell tobacco to minors. In the neighbouring health unit, a high rate of selling continued until a federal program using a similar intervention was implemented, after which a large reduction (from 47% to 2%) was observed. This magnitude of change has been unprecedented, except when active enforcement was implemented by police officers. Thus, from a public health perspective, it is important to understand what is influencing the store operators.", "To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care.\n Both smoking and nonsmoking teens, 14 to 17 years of age, who were being seen for routine visits were eligible for this 2-arm controlled trial. Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group-practice health maintenance organization. Of 3747 teens invited at > or =1 visits, 2526 (67%) consented and were randomized to tobacco intervention or brief dietary advice. The tobacco intervention was individually tailored on the basis of smoking status and stage of change. It included a 30-second clinician advice message, a 10-minute interactive computer program, a 5-minute motivational interview, and up to two 10-minute telephone or in-person booster sessions. The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables. Follow-up smoking status was assessed after 1 and 2 years.\n Abstinence rates after 2 years were significantly higher for the tobacco intervention arm, relative to the control group, in the combined sample of baseline smokers and nonsmokers (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.03-1.47). Treatment effects were particularly strong among baseline self-described smokers (OR: 2.42; 95% CI: 1.40-4.16) but were not significant for baseline nonsmokers (OR: 1.25; 95% CI: 0.97-1.61) or for those who had \"experimented\" in the past month at baseline (OR: 0.95; 95% CI: 0.45-1.98).\n Brief, computer-assisted, tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset.", "The objective of the present study was to study the ability to influence young at-risk patients' attitudes toward tobacco use through two intervention methods that were performed by dental health professionals.\n Two interventions, a brief individual motivational interview and an adapted school lecture, were studied, and both were compared with a control group. Before and after interventions, a questionnaire was used. Patients born in 1989 and 1992 who were judged by the dental personnel as potentially at risk for dental diseases, a total of 301 individuals, were included.\n Both before and after interventions, the results showed a generally negative attitude towards tobacco use. A majority of the participants were positive towards measures that were taken to control the spread of tobacco use, younger participants (born 1992) to a greater extent (73%) than the older participants (born 1989) (54%). Important factors that kept the participants away from tobacco use were the harmful effects and the approaches of parents and friends. The older participants believed to a greater extent that they would try smoking as adults. No change in tobacco use was registered after intervention, although the participants reported an increased use among friends.\n The two pedagogical methods that were used in the present study influenced the young people's attitudes towards tobacco use only to a small extent. However, the period between 12 and 15 years old seems to provide a good opportunity to influence attitudes towards tobacco. The adolescents' demand for interactive learning and their development of attitudes and tobacco use habits in relation to family and friends provide opportunities to use new pedagogical models.", "Adolescent males in rural areas use smokeless tobacco (ST). We assessed the efficacy of a school-based nurse-directed ST intervention among rural high school males.\n Study high schools were randomly selected from a public high school list of California rural counties. Consenting high schools were stratified by school size and randomly assigned within strata to intervention or no-intervention groups. After gaining parental consent, male students completed baseline and 1-year follow-up questionnaires. The intervention included peer-led educational sessions and an oral exam by the school nurse who also provided brief tobacco cessation counseling. We used binary generalized estimating equation (GEE) models accounting for clustering within schools to test no difference between groups after adjusting for year in high school using both completers only and multiple imputation for those lost to follow-up. Subgroup analyses assessed Baseline Factor x Group interaction in GEE models.\n Twenty-one rural counties (72%), 41 randomly selected high schools (56%), and 4,731 male students (50%) participated with 65% retention. Nonsmoking ST users in the intervention group were significantly more likely to stop using ST at follow-up than those in the no-intervention group; there was no intervention effect among baseline ST users who also smoked. A higher percentage of baseline nonsmoking ST users reported smoking at follow-up than baseline non-ST-using smokers who reported using ST.\n A school-based nurse-directed ST cessation program was efficacious among rural nonsmoking ST-using high school males. The potential program reach holds significant public health value. Baseline ST use facilitated smoking at follow-up.", "We assessed the effectiveness of a 2-year multicomponent, school-based intervention designed to reduce tobacco use rates among adolescents in an urban area of India.\n Students from 32 schools in Delhi and Chennai, India, were recruited and randomly assigned to an intervention or control group. Baseline, intermediate, and outcome data were collected from 2 cohorts of 6th- and 8th-grade students in 2004; 14,063 students took part in the study and completed a survey in 2004, 2005, or 2006. The intervention consisted of behavioral classroom curricula, school posters, a parental involvement component, and peer-led activism. The main outcome measures were self-reported use of cigarettes, bidis (small hand-rolled, often flavored, cigarettes), and chewing tobacco and future intentions to smoke or use chewing tobacco.\n Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period. They were also less likely to intend to smoke or chew tobacco in the future.\n School-based programs similar to the intervention examined here should be considered as part of a multistrategy approach to reducing tobacco use among young people in India." ]

[ "10428523" ]

[ "A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis." ]

[ "To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated.\n A multicentre, prospective, randomised controlled study.\n Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery.\n A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis.\n After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years.\n Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups.\n At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427).\n Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis." ]

[ "12850603", "15467557" ]

[ "A randomized controlled trial of prophylactic maneuvers to reduce head-to-body delivery time in patients at risk for shoulder dystocia.", "Randomized trial of McRoberts versus lithotomy positioning to decrease the force that is applied to the fetus during delivery." ]

[ "To assess whether prophylactic use of the McRoberts maneuver and suprapubic pressure decreased the head-to-body time, as a proxy for shoulder dystocia, in at-risk patients.\n Patients with estimated fetal weights over 3800 g were randomized to undergo the McRoberts maneuver and suprapubic pressure before delivery of the fetal head (prophylactic maneuvers) or to undergo maneuvers only after delivery of the head, if necessary (controls). A total of 185 patients were enrolled in the study. After exclusions (eg, abdominal delivery), there were 128 evaluable vaginal deliveries. The study had the power to detect a 30% difference in head-to-body time between groups.\n Head-to-body delivery times did not differ between the prophylactic and control patients (24 +/- 18 seconds versus 27 +/- 20 seconds, P =.38). In addition, the two groups did not differ in rates of admission of the infant to the special care nursery or in birth injuries. There was a significant increase in the risk of delivering by cesarean for patients randomized to the use of prophylactic maneuvers.\n This study does not support the hypothesis that prophylactic use of the McRoberts maneuver and suprapubic pressure speeds delivery in a population of patients at increased risk for shoulder dystocia.", "In an effort to reduce shoulder dystocia incidence and morbidity, some obstetricians use prophylactic maternal hip hyperflexion (McRoberts maneuver), with the hope of facilitating delivery and decreasing the traction needed for delivery. The objective of this study was to evaluate whether the delivery force is reduced with the prophylactic McRoberts maneuver in a prospective, objective manner.\n Between April 2002 and July 2003, we randomly assigned multiparous women with term, cephalic singleton gestations to delivery in the lithotomy or McRoberts position. A single physician used a force-measuring system that consisted of a custom glove with force sensors to record the amount of force that was exerted on the fetal head. The primary outcomes of the study were peak force (pounds; highest force needed to accomplish entire delivery), peak force for delivery of anterior shoulder (pounds), and peak force rate (pounds per second; the duration required to reach the peak force).\n The peak force was not different between the patients in the lithotomy position (n=13) versus the McRoberts position (n=14; 7.2 +/- 0.8 lbs vs 8.0 +/- 0.7 lbs; P = .5). The peak force for delivery of the anterior shoulder (6.7 +/- 0.8 lbs vs 7.1 +/- 0.7 lbs; P = .7) and peak force rate (32.3 +/- 7.0 lbs/sec vs 29.1 +/- 3.5 lbs/sec; P = .7) were not different between the patients in the lithotomy position versus the McRoberts position, respectively. There was no difference between the groups for gestational age, birth weight, incidence of diabetes mellitus, or operative vaginal delivery. The subjective degree of difficulty of the delivery correlated with the peak force (R2 = 0.53; P = .001).\n The use of the McRoberts maneuver before clinical diagnosis of shoulder dystocia provides no reduction in the force that is used in traction on the fetal head during vaginal delivery in multiparous patients. The acceptance of this maneuver to be used prophylactically requires re-evaluation." ]

[ "15235901", "7543781" ]

[ "A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.", "Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis." ]

[ "Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.\n We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).\n Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.\n The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.", "In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intraarterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n = 7) was given G-CSF and group B (n = 7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (< 2,000/mm3). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3: group A-1 (n = 3) and group A-2 (n = 4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis." ]

[ "16735589", "11307071", "10424554" ]

[ "Arthroscopic versus open shoulder stabilization for recurrent anterior instability: a prospective randomized clinical trial.", "Comparison of an arthroscopic and an open procedure for posttraumatic instability of the shoulder: a prospective, randomized multicenter study.", "Prospective randomized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation in first traumatic anterior dislocations of the shoulder." ]

[ "Arthroscopic stabilization for anterior shoulder instability has been reported to result in a higher rate of recurrent instability compared to traditional open techniques.\n To test the null hypothesis that there is no difference in the clinical outcomes in patients with recurrent anterior shoulder instability treated with open or arthroscopic stabilization.\n Randomized controlled trial; Level of evidence, 1.\n A consecutive series of 64 patients with recurrent anterior shoulder instability were randomized to receive either arthroscopic or open stabilization by a single surgeon. Magnetic resonance arthrogram studies were obtained preoperatively. These findings were compared to arthroscopic findings. Postoperative evaluations included range of motion, stability, and subjective assessments including Single Assessment Numeric Evaluation, Simple Shoulder Test, Western Ontario Instability Index, and University of California, Los Angeles evaluation. Failure was defined as a second dislocation, recurrent subluxation, or symptoms precluding return to previous work or unrestricted active military duty.\n Sixty-one patients, 29 who received open stabilization and 32 who received arthroscopic stabilization, were evaluated at a mean of 32 months postoperatively (range, 24-48 months). Patient demographics were equivalent. Preoperative magnetic resonance arthrogram findings were confirmed at arthroscopic examination. The mean operative time was significantly shorter for the arthroscopic repairs (59 vs 149 minutes; P < .001). There were 3 clinical failures (2 open stabilizations, 1 arthroscopic stabilization) by the established criteria. There was a statistically significant improvement from preoperative to postoperative Single Assessment Numeric Evaluation scores in both groups (P < .001). The mean loss of motion (compared to the contralateral shoulder) was greater in the open shoulders. Subjective evaluations were equal in both groups. Conclusion: Clinical outcomes after arthroscopic and open stabilization were comparable. Preoperative magnetic resonance arthrograms in shoulders with anterior instability allow an accurate diagnosis of intra-articular abnormality that correlates well with operative findings. Arthroscopic stabilization for recurrent anterior shoulder instability can be performed safely; the clinical outcomes are comparable to those after traditional open stabilization.", "From 1993 through 1996, a multicenter study was conducted on the surgical treatment of patients with posttraumatic recurrent anterior shoulder dislocations. Fifty-six patients (40 men, 16 women; mean age 26 years [range 18-51 years]), were evaluated with shoulder arthroscopy. If a Bankart lesion was present, the patients were randomly allocated to either an arthroscopic reconstruction with the use of biodegradable tacks or an open reconstruction with suture anchors. The postoperative rehabilitation protocol for the two groups was identical. In all patients, the range of shoulder motion, stability, and the Constant and Rowe scores were evaluated at 3, 12, and 24 months postoperatively. Thirty patients were surgically treated with the arthroscopic technique and 26 patients with the open technique. In the arthroscopic group, there were recurrences in 7 (23%) of 30 patients at a mean of 13 months (range 5 to 21 months) after surgery. All patients with stable shoulders had a negative apprehension test result. In the open group, there were recurrences in 3 (12%) of 26 patients at a mean of 10 months (range 2 to 23 months) after surgery (P = not significant). In the arthroscopic group, 2 patients had new traumatic redislocations, whereas 1 patient redislocated during an epileptic seizure. In the open group, 1 traumatic redislocation occurred. The 2-year results in this study demonstrate a large number of redislocations after reconstruction, even in the open surgery group. Patient noncompliance with the rehabilitation protocol and predisposing disease may partially explain these results. A tendency was seen toward more redislocations in the arthroscopic group, which emphasizes the importance of correct patient selection and careful surgical technique in the difficult surgical procedure.", "Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder. Forty skeletally mature patients younger than 30 years of age were randomly allocated to immobilization for 3 weeks followed by rehabilitation (group T) or arthroscopic stabilization (within 4 weeks of injury) followed by an identical immobilization and rehabilitation protocol (group S). A blinded research assistant performed all follow-up evaluations. The dominant arm was involved in 35% of subjects. The injury occurred in a sporting event in 70% of subjects. At 24 months, there was a statistically significant difference in the rate of redislocation (T = 47%, S = 15.9%, P = .03). An intention-to-treat analysis comparing disease-specific quality of life using the validated Western Ontario Shoulder Instability (WOSI) index showed statistically significantly better results in the surgically treated group at the 33 months (T = 633.93 v S = 287.1, P = .03) and no significant difference in range of motion. At an average 32 months follow-up, a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first, traumatic, anterior dislocation of the shoulder." ]

[ "9523803", "11159241", "10714841", "9523805", "10757577", "11167171", "9523804", "11159240", "11012500", "10834773", "12594142", "8519711", "18326251", "9698950", "11394516", "1594260" ]

[ "Transient neurologic symptoms after spinal anesthesia with mepivacaine and lidocaine.", "Transient neurologic symptoms after spinal anesthesia with lidocaine in obstetric patients.", "The incidence of transient neurologic symptoms (TNS) after spinal anaesthesia in patients undergoing surgery in the supine position. Hyperbaric lidocaine 5% versus hyperbaric bupivacaine 0.5%.", "Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.", "A randomised study of lidocaine and prilocaine for spinal anaesthesia.", "Transient neurologic symptoms after spinal anaesthesia using isobaric 2% mepivacaine and isobaric 2% lidocaine.", "Incidence of transient neurologic symptoms after hyperbaric subarachnoid anesthesia with 5% lidocaine and 5% prilocaine.", "Does pregnancy protect against intrathecal lidocaine-induced transient neurologic symptoms?", "The incidence of transient neurological symptoms after spinal anaesthesia with lidocaine compared to prilocaine.", "Procaine compared with lidocaine for incidence of transient neurologic symptoms.", "Urinary bladder scanning after day-case arthroscopy under spinal anaesthesia: comparison between lidocaine, ropivacaine, and levobupivacaine.", "Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine.", "[Transient neurological symptoms in puerperas after epidural analgesia during labor].", "Transient radicular irritation after spinal anesthesia induced with hyperbaric solutions of cerebrospinal fluid-diluted lidocaine 50 mg/ml or mepivacaine 40 mg/ml or bupivacaine 5 mg/ml.", "Spinal anesthesia: a comparison of procaine and lidocaine.", "Lidocaine test in neuralgia." ]

[ "Spinal anesthesia with lidocaine is ideal for ambulatory surgery because of its short duration of action. However, transient neurologic symptoms (TNS) occur in 0-40% of patients. The incidence of TNS with mepivacaine, which has a similar duration of action, is unknown.\n Sixty ambulatory patients undergoing knee arthroscopy received spinal anesthesia in a randomized, double-blinded manner, with either 45 mg 1.5% mepivacaine or 60 mg 2% lidocaine. An L3-L4 midline approach was used with a 27-gauge Whitacre needle and a 20-gauge introducer. The local anesthetic was injected over approximately 30 s with the aperture of the Whitacre needle in a cephalad direction. Two to 4 days after operation, each patient was questioned about the development of TNS. In addition, the two groups were compared for time to regression of sensory and motor blockade and time to discharge milestones.\n Three patients receiving lidocaine were lost to follow-up. None of the 30 patients in the mepivacaine group developed TNS, whereas 6 of 27 (22%) in the lidocaine group did (P = 0.008). Time to regression to the L5 sensory level and to complete resolution of motor block were similar in both groups. The times to discharge milestones were also comparable.\n The incidence of TNS is greater with 2% lidocaine than with 1.5% mepivacaine for patients having unilateral knee arthroscopy under spinal anesthesia. Mepivacaine seems to be a promising alternative to lidocaine for outpatient surgical procedures because of its similar duration of action. Further studies are warranted to determine the optimal dose of intrathecal mepivacaine for ambulatory surgery and the incidence of TNS with other doses and concentrations of intrathecal mepivacaine.", "We investigated the relationship between intrathecal lidocaine and transient neurologic symptoms in the obstetric population because lidocaine spinal anesthetics are commonly used for various obstetric procedures, and little has been reported in this regard from within this population. In this study, 58 ASA physical status I patients presenting for postpartum bilateral tubal ligation under spinal anesthesia were randomized to receive either hyperbaric 5% lidocaine or 0.75% bupivacaine in a double-blinded manner. All patients were in the supine position for their surgery. Postoperatively, all patients were followed by a blinded investigator using a standardized symptom checklist. The incidence of transient neurologic symptoms with lidocaine was 3% (95% confidence interval = 0.1%--17.8%) and that with bupivacaine was 7% (95% confidence interval = 0.9%--23.5%), (P = not significant). Symptoms consistent with this syndrome occurred within 24 h without any associated sensory or motor deficits or functional impairment, and resolved within 48 h without any intervention.", "The incidence of TNS after spinal anaesthesia is a problem. Especially the use of hyperbaric lidocaine in patients placed in the lithotomy position during surgery has been associated with a high incidence of TNS. The present study was performed to investigate whether TNS is present more frequently in patients undergoing surgery in the supine position with use of hyperbaric lidocaine compared with hyperbaric bupivacaine.\n Seventy patients were included and randomised to receive either hyperbaric lidocaine or hyperbaric bupivacaine. All patients were contacted on the first and third postoperative days by an anaesthesiologist blinded to the local anaesthetic used. The patients were asked about symptoms of TNS, pain not associated with the operation area, and asked to grade the complaints after a verbal analogue score from 0 to 10.\n We found a total of ten patients who showed signs of TNS. There were nine patients in the lidocaine group (26%) who showed signs of TNS compared to only one patient in the bupivacaine group (3%) (P<0.01). The average score of TNS complaints was 3.5. A total of 13 patients (19%) complained of back pain. There were no significant differences with regard to which local anaesthetic was used. The average score of back pain was 3.3.\n TNS is a significant problem in patients having spinal anaesthesia with hyperbaric lidocaine compared to hyperbaric bupivacaine, both in the supine position. For day-case surgery, TNS would start after dismissal from hospital. The use of hyperbaric lidocaine is therefore questionable, even though these problems are of an order that the majority of patients would still choose spinal anaesthesia for future operations.", "Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs.\n Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure.\n Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05).\n Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "Transient neurologic symptoms (TNS) are common after lidocaine-induced spinal anaesthesia (SA). Recent data indicate that TNS may be less frequent after prilocaine-induced spinal anaesthesia, for which reason the isobaric solution was compared with lidocaine.\n One hundred patients scheduled for short urologic procedures under spinal anaesthesia were randomised to receive 80 mg prilocaine or lidocaine, both 20 mg/ml. The clinical course and the duration of anaesthesia were monitored. The following day an anaesthesiologist unaware of the randomisation interviewed the patients using a structured questionnaire.\n Following prilocaine spinal anaesthesia the mean time until 2-segment regression was 123(SD 42) min and total sensory block lasted 221(49) min, compared to 106(26) and 181(48) min following lidocaine. TNS occurred in 7/49 patients in the lidocaine group and in 2/50 in the prilocaine group (ns).\n TNS occurred also after isobaric prilocaine SA. The frequency was not significantly different from that following lidocaine SA but larger studies are needed to establish the relative risk of TNS following SA induced by the two local anaesthetics. Isobaric prilocaine has a longer duration of action than an equal dose of lidocaine and may be an alternative drug for spinal anaesthesia of intermediate or short duration.", "Transient Neurological Symptoms (TNS) syndrome following subarachnoid anaesthesia was initially associated with hyperbaric lidocaine 50 mg/ml, but has also been reported with most local anaesthetics, including hyperbaric mepivacaine 40 mg/ml. The aim of this study was to determine the incidence of TNS after subarachnoid anaesthesia using isobaric mepivacaine 20 mg/ml and isobaric lidocaine 20 mg/ml.\n Eighty patients of both sexes, ASA class I-II, scheduled for elective minor orthopaedic surgery under subarachnoid anaesthesia, were prospectively included and randomly allocated to receive 40-60 mg of either isobaric mepivacaine 20 mg/ml (Group M) or isobaric lidocaine 20 mg/ml (Group L). Patients were evaluated on the first postoperative day by one investigator unaware of the grouping, looking for symptoms suggestive of TNS, such as pain or dysaesthesias in the buttocks or lower limbs with or without back pain.\n TNS symptoms were observed in three patients (7.5%) of Group M and in one patient (2.5%) of Group L, without statistically significant differences between the groups. Symptoms had an abrupt onset and relief, lasted from 45 min to 24 h, and had a complete resolution without sequelae. The only statistically significant difference between groups was longer motor blockade in Group M (P=0.0031).\n In this study TNS was associated with isobaric mepivacaine 20 mg/ml, with an incidence of 7.5%, and with isobaric lidocaine 20 mg/ml, with an incidence of 2.5%, in patients having orthopaedic procedures in the supine position.", "Hyperbaric 5% lidocaine has been associated with transient neurologic symptoms (TNSs) after spinal anesthesia. A prospective, masked, randomized study was conducted to compare the incidence of TNSs after spinal anesthesia with hyperbaric 5% lidocaine or 5% prilocaine to assess the utility of prilocaine as an alternative to lidocaine in patients having short surgical procedures.\n The number of patients to be enrolled (100 per group) was determined by power analysis (80%, P = 0.05) considering an incidence of TNSs after spinal anesthesia with lidocaine of at least 11% according to data reported in other studies. Two hundred patients scheduled for elective surgery expected to last <60 min were allocated at random to receive spinal anesthesia with hyperbaric 5% lidocaine or hyperbaric 5% prilocaine. Three to 5 days after spinal anesthesia, all patients were interviewed by an anesthesiologist who was blinded to the group assignment and details of the anesthetic and surgical technique using a standardized symptom checklist. Patients with symptoms underwent neurologic examination.\n Both groups were comparable with regard to demographic data and details of the surgical and anesthetic procedures. The incidence of TNSs in both groups was low and differences were not found (4% in the lidocaine group and 1% in the prilocaine group). The mean age of patients with TNSs (58 yr) was higher than that of patients without TNSs (48 yr; P < 0.05). No relation with any of the other variables was found.\n The low incidence of TNSs among lidocaine-anesthetized patients (4%) may account for the lack of significant differences between hyperbaric 5% lidocaine and 5% prilocaine and to the insufficient power of the study to exclude the possibility of a type II error.", "We investigated the incidence of transient neurologic symptoms (TNS) after the use of hyperbaric lidocaine as compared with hyperbaric bupivacaine in patients undergoing cesarean delivery under spinal anesthesia. Two hundred women scheduled for cesarean delivery were randomly allocated to receive spinal anesthesia with 75 mg hyperbaric lidocaine 5% (n = 100) or 12 mg hyperbaric bupivacaine 0.75% (n = 100). Spinal anesthesia was administered to all patients in the sitting position with a 25-gauge Whitacre needle. The level of sensory blockade, time to full recovery, and intraoperative hemodynamic profile were noted in all patients. The patients were interviewed postoperatively for three consecutive days to detect the occurrence of TNS. The incidence of TNS was zero (95% confidence interval 0%--3%) in both the Lidocaine and the Bupivacaine Groups. Our results indicate that the frequency of postoperative TNS does not exceed 3% in patients undergoing cesarean delivery at term using hyperbaric lidocaine 5% or hyperbaric bupivacaine 0.75%.", "The purpose of this double-blind study was to investigate the incidence of transient neurological symptoms after the use of isobaric lidocaine and isobaric prilocaine for spinal anaesthesia. Seventy patients (ASA 1-2, age between 18 and 70 years) were randomly assigned to two groups of 35 patients each, to receive either isobaric 2% lidocaine 4 ml or isobaric 2% prilocaine 4 ml intrathecally, at the L3-4 interspace. One patient in the prilocaine group could not be included because data were incomplete. On the first postoperative day, patients were evaluated for transient neurological symptoms. Pain was scored on a 10-point scale. Seven patients (20%) in the lidocaine group had transient neurological symptoms with a mean pain score of 5.3, whereas no patient in the prilocaine group had these complaints (p = 0.006). Symptoms disappeared within 4 days. Prilocaine results in a lower incidence of transient neurological symptoms than lidocaine intrathecally and therefore it is more suitable for short surgical procedures.", "Transient neurologic symptoms (TNS) have been reported to occur after 16% to 40% of ambulatory lidocaine spinal anesthetics. Patient discomfort and the possibility of underlying lidocaine neurotoxicity have prompted a search for alternative local anesthetic agents. We compared the incidence of TNS with procaine or lidocaine spinal anesthesia in a 2:1 dose ratio.\n Seventy outpatients undergoing knee arthroscopy were blindly randomized to receive either 100 mg hyperbaric procaine or 50 mg hyperbaric lidocaine. An interview by a blinded investigator established the presence or absence of TNS, defined as pain in the buttocks or lower extremities beginning within 24 hours of surgery. Onset of sensory and motor block, patient discomfort, supplemental anesthetics, and side effects were recorded by the unblinded managing anesthesia team. Anesthetic adequacy was determined from these data by a single blinded investigator. Hospital discharge time was recorded from the patient record. Groups were compared using appropriate statistics with a P < .05 considered significant.\n TNS occurred in 6% of procaine patients versus 31% of lidocaine patients (P = .007). Sensory block with procaine and lidocaine was similar, while motor block was decreased with procaine (P < .05). A trend toward a higher rate of block inadequacy (17% v 3%, P = .11) and intraoperative nausea (17% v 3%, P = .11) occurred with procaine. Average hospital discharge time with procaine was increased by 29 minutes (P < .05).\n The incidence of TNS was substantially lower with procaine than with lidocaine. However, procaine resulted in a lower overall quality of anesthesia and a prolonged average discharge time. If the shortfalls of procaine as studied can be overcome, it may provide a suitable alternative to lidocaine for outpatient spinal anesthesia to minimize the risk of TNS.", "Micturition problems after spinal anaesthesia may delay hospital discharge. The use of lidocaine has raised concerns because of the occurrence of transient neurological symptoms (TNS). This randomized double-blind study was designed to compare the newer local anaesthetics with lidocaine regarding block characteristics, micturition problems, and discharge times in day-case spinals for arthroscopy.\n Ninety patients received either isobaric lidocaine 60 mg, ropivacaine 15 mg, or levobupivacaine 10 mg intrathecally. Urinary bladder volumes were measured by ultrasound imaging at regular time intervals until a post-voiding residual volume (PVRV) less than 100 ml was obtained. Micturition problems were classified in five groups ranging from no problems to those requiring catheterization.\n Times to regain a Bromage-1 and -0 motor block were similar in the three groups but sensory block regression to L2 occurred at 145 (30) min in the lidocaine group, 25-30 min (P<0.05) faster than the other groups. Lidocaine allowed voiding after 245 (65) min and hospital discharge 265 (70) min after spinal injection, 40 min faster than in the two other groups. The incidence or degree of micturition problems were not different between after discharge, three patients (10%) receiving lidocaine complained of symptoms compatible with TNS.\n Our study suggested that the three local anaesthetics behave similar regarding quality of anaesthesia and motor block but voiding and discharge occurred significantly earlier with lidocaine although the 40 min difference was not impressive considering a spinal discharge time interval of 4-5 h.", "In addition to major neurologic injury, local anesthesia toxicity may also include less severe but more common neurologic side effects. The authors recently observed symptoms suggestive of transient radicular irritation in one third of patients after spinal anesthesia with hyperbaric 5% lidocaine, whereas evidence of neurologic symptoms was lacking with hyperbaric 0.5% bupivacaine. The purpose of this prospective double-blinded study was to evaluate if the high osmolarity of hyperbaric 5% lidocaine solution might contribute to the development of transient radicular irritation.\n Forty-four patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1.5 mL of one of three study drugs: 5% lidocaine in 7.5% dextrose (drug A), 0.5% bupivacaine in 8.25% dextrose (drug B), or 5% lidocaine in 2.7% dextrose (drug C). Drug C was prepared by the pharmacy (University Hospital, Basel, Switzerland) with an osmolarity similar to that of drug B. Drugs A and B were commercially available. Patients were evaluated on postoperative day 1 for symptoms of transient radicular irritation by an anesthesiologist who was unaware of the drug given or details of the anesthetic technique.\n Symptoms suggestive of transient radicular irritation were observed with a similar high incidence in patients receiving both lidocaine preparations, but in no patient receiving hyperbaric 0.5% bupivacaine (P < .01).\n The results suggest that transient radicular irritation did not result from the marked hyperosmolarity of the hyperbaric 5% lidocaine. However, because lidocaine and bupivacaine were not administered at equipotent dosages, the relative potential for both drugs to induce transient radicular irritation remains to be determined.", "The investigation was undertaken to elucidate the impact of epidural analgesia (EA) during labor on the incidence of transient neurological symptoms (TNS). By the agreement of a local ethics committee, an informed consent was obtained from 90 healthy puerperas enrolled in the investigation. The patients were randomized into 3 groups, with 30 patients in each. At the beginning of labor, an epidural catheter was inserted in all the puerperas. For EA, 1% lidocaine solution and 0.2% ropivacaine solution were used in Groups 1 and 2, respectively; Group 3 was control in which EA was not performed. Two days after labor, an independent observer asked the females about possible neurological symptoms, by using the standard questionnaire. TNS included symmetric pain and/or dysesthesia in the buttocks, lower lumbar region, and/or legs. The patients who presented problems were proposed to indicate the degree of discomfort by a 10-score verbal scale. The findings were statistically processed using the U-test and X-test (p < 0. 05). A total of TNS occurred in 22 (25%) patients, including 7 (27%), 8 (27%), and 7 (23%) in Groups 1, 2, and 3, respectively. This difference was not statistically significant. The duration of TNS was generally short; in all the patients, the symptoms were completely resolved after 24-72 hours. Labor EA is not a cause of TNS. The type of a local anesthetic (lidocaine, ropivacaine) does not affect the incidence of TNS in puerperas after labor EA.", "Transient radicular irritation (TRI) is common after spinal anesthesia induced with hyperbaric lidocaine 50 mg/ml. The purpose of this study was to determine the incidence of TRI after spinal anesthesia with hyperbaric lidocaine 50 mg/ml diluted with cerebrospinal fluid (CSF) 1:1 and hyperbaric mepivacaine 40 mg/ml and hyperbaric bupivacaine 5 mg/ml.\n Ninety ASA class I-IV patients undergoing mostly brief urological procedures under spinal anesthesia were randomly allocated to receive either hyperbaric lidocaine 50 mg/ml diluted with CSF 1:1 (Group L), hyperbaric mepivacaine 40 mg/ml (Group M) or hyperbaric bupivacaine 5 mg/ml (Group B). Characteristics of the patients and details of the surgical procedures and spinal anesthesias were similar in all groups except for the intensity of motor block. The patients were evaluated on the first postoperative day by an anesthesiologist who did not know which spinal anesthetic agent had been used.\n Six patients (20%) in group L, 11 patients (37%) in Group M and none (0%) in Group B experienced pain in the legs and/or back (TRI) after spinal anesthesia.\n TRI is frequent after spinal anesthesia induced with hyperbaric lidocaine 50 mg/ml diluted with CSF 1:1. The incidence of TRI after hyperbaric mepivacaine 40 mg/ml is of the same magnitude. TRI could not be observed after bupivacaine spinal anesthesia.", "To compare spinal procaine to spinal lidocaine with regard to their main clinical characteristics and incidence of transient radicular irritation (TRI).\n In this randomized, double-blind, prospective study, patients (two groups, n=30 each) received either 100 mg of lidocaine 5% in 7.5% glucose (Group L) or 100 mg of procaine 10% diluted with 1 ml cerebrospinal fluid (Group P). After spinal anesthesia, segmental level of sensory block was assessed by pinprick. Blood pressure and the height of the block were noted each minute for the first ten minutes, then every three minutes for the next 35 min and finally every five minutes until regression of the block to L4. Motor blockade was evaluated using the Bromage scale. To evaluate the presence of TRI, each patient was questioned 48 hr after surgery.\n Time to highest sensory level and to maximum number of segments blocked showed no difference between groups. Mean time for sensory regression to T10 and for regression of the motor block were shorter in Group P. Eighty minutes following injection, sensory levels were lower in Group P. Five patients had inadequate surgical anesthesia in Group P and only one in Group L. No patient in Group P had TRI (95% CI 10-12%) while eight (27%) in Group L did (95% CI 12-46%).\n Procaine 10% was associated with a clinical failure rate of 14.2%. This characteristic must be balanced against an absence of TRI, which occurs more frequently with the use of lidocaine 5%.", "Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables. The variables assessed were the subjective magnitude of pain, area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia. The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain. It was found that spontaneous pain and mechanical hyperalgesia were consistently improved, transiently, by intravenous administration of lidocaine in all 10 patients; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently. Spontaneous pain and mechanical hyperalgesia, but not hypoesthesia, were transiently improved by injection of saline in only 1 of the 10 patients. This outcome is probably due to a placebo effect. This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia. Thus, intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury. The transient pain relief may allow a fuller identification of the area of sensory loss." ]

[ "8878223", "2123239", "8849215", "3057159", "3302916", "3923180", "8637789", "15084807", "7559195", "12075760", "8396102", "14732316", "8945796" ]

[ "Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin V in the treatment of acute streptococcal pharyngitis in children: results of a multicenter, open comparative study. The Swiss Tonsillopharyngitis Study Group.", "Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates.", "Comparative efficacy and safety of 3-day azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children.", "Standardized symptomatic treatment versus penicillin as initial therapy for streptococcal pharyngitis.", "Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin.", "Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis.", "Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG.", "Streptococcal-A tonsillopharyngitis: a 5-day course of cefuroxime axetil versus a 10-day course of penicillin V. results depending on the children's age.", "A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.", "Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis.", "Multicentre evaluation of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis and tonsillitis in children.", "Failure to eradicate Group A beta-haemolytic streptococci (GABHS) from the upper respiratory tract after antibiotic treatment.", "Do patients with sore throat benefit from penicillin? A randomized double-blind placebo-controlled clinical trial with penicillin V in general practice." ]

[ "For many years alternatives to penicillin have been studied for the management of pediatric group A beta-hemolytic Streptococcus (GABHS) pharyngitis. As a result of its pharmacokinetic profile azithromycin is unique among these alternative antimicrobials in allowing once daily dosing and shorter duration of treatment. However, the optimum dose (e.g. 10 or 12 mg/kg/day) and duration (e.g. 3 or 5 days) of azithromycin therapy have not been defined yet.\n An open, comparative multicenter study was conducted in 343 children with clinical symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and safety of azithromycin (10 mg/kg) once daily for 3 days compared with penicillin V three times daily for 10 days.\n Among the evaluable patients bacteriologic eradication documented at follow-up visits was inferior with azithromycin when compared with penicillin V therapy: at Days 9 to 20 (mean, 12 days), negative cultures in 65% (99 of 152 patients) vs. 82% (128 of 126 patients) (P < 0.001); and at Days 17 to 57 (mean, 25 days), in 55% vs. 80% (P < 0.001). Overall clinical success (cure or improvement) was achieved in 93% (149 of 160 patients) of azithromycin-treated and in 89% (143 of 160 patients) of penicillin-treated patients (P > 0.50). There was no correlation between bacteriologic response and clinical outcome, as assessed shortly after completion of therapy or during 6-month follow-up. Both treatments were well-tolerated.\n In the present study on GABHS pharyngitis in children, a once daily (10-mg/kg), 3-day oral regimen of azithromycin was as clinically effective and as safe as traditional penicillin but appeared inferior in eliminating GABHS from the throat.", "To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate.", "The efficacy and safety of a 3-day course of azithromycin oral suspension (10 mg/kg of body weight once daily) were compared with those of penicillin V (50,000 U/kg/day in two divided doses) in children aged 3 to 12 years for the treatment of symptomatic pharyngitis caused by the group A beta-hemolytic streptococcus (GABHS). For the 154 evaluable patients, the original infecting strain of GABHS was eliminated at the end of follow-up (34 to 36 days after treatment started) from 67 (85.8%) of 78 penicillin-treated patients and 41 (53.9%) of 76 azithromycin-treated patients (P < 0.0001). Overall clinical success was achieved in 71 (91.0%) of 78 penicillin V-treated patients and 57 (75.0%) of 76 azithromycin-treated patients (P < 0.05). Potential drug-related adverse events were reported for 5.5 and 8.6% of the penicillin V- and azithromycin-treated patients, respectively (P = 0.6). In the present study, a once-daily (10 mg/kg), 3-day oral regimen of azithromycin was as safe as a 10-day course of penicillin but did not represent an effective alternative to penicillin for the treatment of GABHS pharyngitis, even for those children with azithromycin-susceptible strains.", "A multicenter, double-blind, randomized, placebo-controlled trial was conducted to determine whether the addition of penicillin was superior to patient education and anti-inflammatory drug therapy for relief of the acute discomforts of pharyngitis caused by group A beta-hemolytic streptococcus (GABHS). One hundred seventy-eight patients, aged 4 to 29 years, received appropriate symptomatic therapy, including specific doses of aspirin or acetaminophen, plus penicillin (91 patients) or placebo (87) for the initial 48 hours of illness. All had 24-hour office and 48-hour telephone reevaluations. In 123 patients (57 with clinically severe pharyngitis), throat cultures yielded GABHS. Penicillin provided a margin of 20% improvement over anti-inflammatory therapy for the complaint of sore throat only after 48 hours of treatment (for the 123 patients with GABHS, p = 0.01; for the 57 with both severe pharyngitis and GABHS, p = 0.05). No significant improvement was noted for fever, malaise, odynophagia, exudate, adenitis, or pharyngitis. The failure of penicillin to provide much additional benefit makes its routine early prescription specifically for symptomatic relief questionable.", "One hundred forty-two children with presumed Group A beta-hemolytic streptococcal (GABHS) pharyngitis were enrolled in a randomized double blind prospective study comparing the consequences of immediate penicillin treatment with treatment delayed for 48 to 56 hours. One hundred fourteen of the enrolled patients were culture-positive. An adverse impact of early antibiotic therapy was noted; the incidence of subsequent infections with GABHS was significantly greater in those treated at the initial office visit with penicillin. In the month following documented evaluation of GABHS, a recurrence occurred 2 times more frequently in those treated with penicillin immediately compared with those for whom treatment was delayed 48 to 56 hours. Late recurrences (beyond 1 month but in the same streptococcal season) occurred 8 times more frequently (P less than 0.035). Delay in penicillin treatment did not increase GABHS intrafamilial spread. Symptoms of both groups were assessed for 2 days following the initiation of treatment. Both placebo-treated and penicillin-treated groups used aspirin or acetaminophen ad libitum. Penicillin was shown to reduce fever and relieve sore throat, dysphagia, headache, abdominal pain, lethargy and anorexia significantly beyond that achieved with aspirin or acetaminophen alone. Penicillin had no effect on culture-negative cases.", "We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal (GABHS) pharyngitis in 260 children. After a throat culture had been obtained, each child was evaluated for the presence of predetermined signs and symptoms, and was then randomized in a double-blind manner to receive penicillin V, cefadroxil, or placebo. Of the 194 children with throat cultures positive for GABHS, 68 received penicillin V, 70 received cefadroxil, and 56 received placebo. Approximately 18 to 24 hours later, each patient returned for reevaluation. Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo. In addition, the evaluating physician, parents, and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement.", "This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers?\n Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG.\n The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand.\n Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt.", "The recommended duration of antibiotic treatment of tonsillopharyngitis caused by group A beta-hemolytic streptococci (GABHS) with penicillin V (PenV) is mostly 10 days. However, compliance with 10-day courses is bad. Shorter therapeutic courses are necessary, especially in young children.\n In a prospective, randomized, multi-center study, children aged 1-17 years with acute tonsillopharyngitis and a positive culture for GABHS were treated with cefuroxime axetil (CAE) 20 mg/kg/day (max. 500 mg) b.i.d. for 5 days or with PenV 50,000 IU/kg (30 mg/kg) t.i.d. for 10 days. Patients were evaluated for clinical efficacy 2-4 and 7-9 days after the end of therapy. Throat swabs were taken 2-4 days after the end of therapy and at the first follow-up visit. Follow-up visits were carried out 7-8 weeks, 6 months and 12 months after study inclusion.\n 1,952 patients (CAE for 5 days, 496 patients/PenV for 10 days, 1,456 patients) could be included in the intent-to-treat analysis. Two to 4 days after completion of the treatment course, the bacteriological eradication in group A (1-5 years) and group B (6-17 years) was 90.52 and 89.53% (CAE) vs. 84.13 and 84.20% (PenV), respectively; p = 0.0172; 0.0382; clinical success was 98.30% (CAE) versus 93.25% (PenV), p = 0.0017. Recurrent infections were significantly higher in younger children (group A) under both treatment regimens. Poststreptococcal sequelae (glomerulonephritis) were observed in only 1 case, in the PenV group.\n CAE b.i.d. for 5 days was at least as effective as PenV t.i.d. for 10 days. Incountries with a low incidence of rheumatic fever, CAE for 5 days can be recommended for the therapy of tonsillopharyngitis due to GABHS - also in young children.\n Copyright 2004 S. Karger AG, Basel", "A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)", "Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results. This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V.\n This was a prospective, comparative, randomized, multicenter trial. Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment. Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates.\n Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis. Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound. On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints. The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%); P < 0.0001]. Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity. Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group).\n This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis.", "Of 96 children (aged 2-12 years) with either acute pharyngitis or acute tonsillitis, 49 received a single daily dose of azithromycin 10 mg/kg (maximum 500 mg) for three days, and 47 received penicillin V at a dose of 125 mg or 250 mg qid (depending on body weight) for ten days. Clinical assessments and laboratory safety tests were performed during and after therapy. Before enrollment, all patients were screened for group A beta-haemolytic streptococci (GABHS) with a rapid test, and a throat swab was taken for confirmatory culture. The presence of GABHS at baseline was confirmed in 41 azithromycin- and 44 penicillin V-treated patients. Cure or improvement was seen in 98% and 100% of azithromycin- and penicillin V-treated patients, respectively. At day 11, bacterial eradication was achieved in 39/41 (95%) azithromycin-treated patients, 38 (93%) of whom were considered clinically cured, while one patient (2%) relapsed. In the penicillin V group, 42/44 (95%) had GABHS eradicated, with 41 (93%) clinically cured and three patients (7%) improved. The remaining two patients in each group were clinically cured despite persistence of Streptococcus pyogenes. At follow-up evaluation (day 30), re-occurrence was observed in 5/37 (14%) and 3/40 (8%) of azithromycin- and penicillin V-treated patients, respectively; all patients were asymptomatic. Both drugs were well-tolerated with only two patients in the azithromycin group complaining of side effects. Treatment related laboratory test abnormalities were observed in 6/47 (13%) and 4/45 (9%) azithromycin- and penicillin V-treated patients, respectively, but none was judged to be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)", "The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue.", "The effect of antibiotic therapy in sore throat is questionable and this dilemma has been complicated by the emergence of multiple resistant strains of micro-organisms.\n A randomized double-blind placebo-controlled clinical trial was undertaken in patients aged 4-60 years to assess the efficacy of penicillin V on the clinical course and bacteriological response in patients with sore throat in general practice.\n Two hundred and thirty-nine patients presenting with an acute sore throat to 37 general practices in the Netherlands who were clinically suspected of group A beta-haemolytic streptococci (GABHS) were randomized for treatment with penicillin V (n = 121) or placebo (n = 118). Resolution of sore throat, fever and return to daily activities were evaluated by the general practitioner 2 days after the start of treatment and by the patients keeping a diary for 7 days. The result of throat culture after 2 days was evaluated.\n A difference in resolution of sore throat was present after 2 days in all patients, but was a result of GABHS-positive patients (n = 111; 46%) in favour of those randomized for penicillin V (adjusted odds ratio 5.3; 95% CI 1.9-15.1). An effect in the course of fever was also seen in GABHS-positive patients (adjusted odds ratio 5.3; 95% CI 1.02-27.7). A difference of 1-2 days was seen in clinical recovery. No difference was found in daily activities between the treatment groups. After 2 days, 4% of the penicillin-treated patients harboured GABHS compared with 75% of the placebo group.\n Only GABHS-positive patients benefit from penicillin V in their clinical cure in the first few days. Therefore, rapid testing is necessary. Treatment may be beneficial with regard to the clinical course, but it is not necessary." ]

[ "7724098", "9351414", "6378516", "299462" ]

[ "Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial.", "Effects of prostaglandin treatment and paracervical blockade on postoperative pain in patients undergoing first trimester abortion in general anesthesia.", "Randomized comparison of prostaglandin treatment in hospital or at home with vacuum aspiration for termination of early pregnancy.", "Use of prostaglandin, hypertonic saline and oxytocin for second-trimester abortion." ]

[ "To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects.\n Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis.\n The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills.\n Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.", "The postoperative analgesic efficacy of a paracervical blockade (PCB) as an adjunct to general anesthesia (GA) during outpatient abortion (dilatation and curettage) is unclear, and the present study was initiated to evaluate if PCB is of significant importance per- or postoperatively.\n Two hundred women (aged 18-49 years) were assigned to one of four groups; group 1 received vaginal prostaglandin (PG) (PGE1, gemeprost 1 mg) for softening of the cervix preoperatively and surgery was performed in GA, group 2 received preoperative PG and surgery was performed in GA + PCB; group 3 did not receive PG treatment and surgery was performed in GA and group 4 were subjected to GA + PCB without preoperative PG.\n Women receiving preoperative prostaglandin treatment (groups 1 and 2) reported significantly higher pain intensity already preoperatively, but also postoperatively as compared to patients not treated with PG. The patients subjected to prostaglandin treatment (groups 1 and 2) also had a significantly higher consumption of analgesics as compared to non-PG treated groups (3 and 4). The addition of PCB did not influence pre- and postoperative pain intensity significantly or consumption of analgesics. Patients receiving PG also reported significantly more nausea than the others although nausea was of low intensity. Patients receiving PG were, however, discharged earlier than the others from the hospital.\n Preoperative treatment of the cervix with prostaglandins was associated with significantly higher pain intensity both pre- and postoperatively, and increased need for analgesics postoperatively and more intense nausea. PCB given just before surgery did not result in significant postoperative analgesia. More efficient techniques for pain control should be developed for women subjected to first trimester abortion with preoperative PG treatment.", "In the present study the efficacy and the acceptability of vaginal administration of a prostaglandin E analogue (9-deoxo-16, 16-dimethyl-9-methylene-PGE2) in hospital or at home were randomly compared with vacuum aspiration for termination of very early pregnancy. Prerequisites for acceptance of the patients were a normal pregnancy, a duration of amenorrhea of 49 days or less, at least one previous full-term pregnancy, and a healthy status. Fifty-three patients fulfilled these criteria and adhered to the protocol. Seventeen patients were treated with prostaglandin at home, 18 with prostaglandin in the hospital (9-methylene-PGE2, 50 to 60 mg twice at 6-hour intervals), and 18 with vacuum aspiration. Each patient was interviewed twice by a trained female psychologist before the treatment and two weeks after. Both the surgical and the nonsurgical methods (at home and in the hospital) were found to be equally effective in terms of frequency of complete abortion. Prostaglandin therapy was associated with a higher frequency of gastrointestinal side effects, pain, and a longer duration of bleeding than was the surgical procedure. The acceptability study showed that prostaglandin treatment was positively received. The patients who were treated with prostaglandin remained very positive after the abortion; a majority of these patients intended to use the same procedure in case of a repeated abortion, and would also recommend the treatment to a relative or a friend. The results of the present study indicate that termination of early pregnancy by a medical method, even if self-administered, is an acceptable procedure at least in selected patients. Further efforts to improve the treatment seem therefore justified.", "The management of second-trimester abortion is still not satisfactory with respect to safety and side-effects; it is considered to be in a state of evolution. The goal of this investigation has been to combine, in reduced quantity, prostaglandin and hypertonic saline in order to minimize the complications and side-effects associated with the separate administration of each component. This study documents the results of a random sample of 385 abortions performed in the second trimester, induced by intra-amniotic instillation of prostaglandin (20 mg) and NaCl 5 and 10 g in different volumes and concentrations augmented with oxytocin. In a series of 20 patients, the coagulation profile is presented and the clinical characteristics of 4 groups are compared. This study demonstrated no coagulation defects. The gastrointestinal side-effects were reduced. In spite of the reduced dosage of each component, the instillation abortion interval still remained 17.08 h on the average. Incomplete abortion ranged from 32% to 48.78%. The data presented in this report suggests that combination of prostaglandin, hypertonic saline and oxytocin is feasible for midtrimester abortion." ]

[ "18434189", "10549990", "19462303", "17511748", "11825860", "21990176", "17165363", "10093649", "12681528" ]

[ "An open randomized study of the treatment of escitalopram alone and combined with gamma-hydroxybutyric acid and naltrexone in alcoholic patients.", "Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine.", "Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study.", "Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study.", "Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal.", "Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial.", "Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptionst.", "[Gamma-hydroxybutyrate for treatment of alcohol withdrawal syndrome in intensive care patients. A comparison between with two symptom-oriented therapeutic concepts].", "Gamma-hydroxybutyric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study." ]

[ "gamma-hydroxybutyric acid (GHB) and the selective serotonin reuptake inhibitor escitalopram are effective in inducing and maintaining abstinence in alcohol. Naltrexone (NTX), an opioid antagonist, may be effective in preventing relapse in alcohol-dependent subjects. To evaluate whether each drug and its combination help to maintain alcohol abstinence, we determined the relapse rate over 6 months in 3 groups of patients. Group 1 (11 patients) received escitalopram (20 mg/day) orally administered; group 2 (12 patients) received NTX (50 mg/day) and escitalopram (20 mg/day); group 3 (12 patients) received GHB (75 mg/kg body weight) and escitalopram (20 mg/day); and group 4 (12 patients) received NTX (50mg/day) plus GHB (75 mg/kg) and escitalopram (20 mg/day). All groups received psychological support and underwent urine tests for alcohol metabolites twice a week. In group 1 (escitalopram only), 6 patients relapsed within 3 months and 3 after 6 months; whereas 2 patients remained abstinent. In group 2 (SSRI+NTX), 5 patients relapsed after 3 months and 3 after 6 months; whereas 4 patients remained abstinent. In group 3 (GHB+SSRI), 3 patients relapsed after 3 months and 3 after 6 months; whereas 6 patients remained abstinent. Finally, in group 4 (NTX+GHB+SSRI), 1 patient relapsed after 3 months and 1 after 6 months, whereas 10 patients remain abstinent. In conclusion, the combination of NTX+GHB+SSRI was the most effective in preventing relapses.", "Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.\n Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed.\n Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.\n GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management.", "Clomethiazole (CLO) has been shown to be effective in treating alcohol withdrawal syndrome (AWS). Gamma-Hydroxybutyric acid (GHB) has also been introduced in the treatment of alcoholic patients and is effective in surgical intensive care unit (ICU) patients in preventing and treating AWS. There are no comparative studies between CLO and GHB in a medical ICU setting.\n Twenty-six alcoholic patients with severe AWS and concomitant medical diseases were randomally enrolled in the study. CLO was given orally to 12 patients in a dosage of 250 mg every 4 hours as a liquid; GHB (initially 30 mg/kg body weight (BW) followed by 15 mg/kg BW) was administered intravenously to 14 patients. Four major AWS symptoms (tremor, sweating, nausea, restlessness) were scored, and the administration of additional medication was registered.\n GHB was more effective in treating AWS symptoms. In the GHB group, AWS score dropped from 6.6 +/- 2.6 to 1.8 +/- 2.1 (p <.01), while in the CLO group, the score dropped from 6 +/- 2.5 to 4.1 +/- 2.4 (n. s.). Differences between groups were significant (p =.021, two-way ANOVA). The treatment did not alter outcome or the duration of ICU stay. No serious side effects were detected.\n GHB effectively controls AWS symptoms in medical ICU patients. The rapid initial treatment response of GHB in contrast to CLO has no influence on duration of patient withdrawal.", "Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side-effect profile.\n The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6-day treatment of alcohol withdrawal in a 4-site, double-blind, randomized, placebo-controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004.\n No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups.\n Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti-craving effect. Therefore, well-designed investigations with larger cohorts are required to further elucidate this issue.", "The aim of this double-blind, comparative study was to assess the efficacy and safety of gamma-hydroxybutyrate (GHB) in ameliorating the symptoms of alcohol withdrawal. Newly admitted alcohol-dependent patients (n = 98) were randomized to receive either clomethiazole 1000 mg daily (CLO group) (n = 33), or 50 mg GHB/kg body wt (n = 33) or 100 mg GHB/kg body wt (n = 32). This dose was administered for 5 days, halved on day 6, and on days 7 and 8 only placebo was given. As CLO is available as capsules and GHB as syrup, a double-dummy method was used to try to ensure blindness. The groups were matched in terms of baseline demographic and alcohol-related variables. There was no difference between the three treatments in ratings of alcohol withdrawal symptoms nor requests for additional medication. After tapering off the active medication, there was no increase in withdrawal symptoms, indicating that physical tolerance did not develop to either GHB or CLO within the 5-day treatment period. The most frequently reported side-effect of GHB was transient vertigo, particularly after the evening double dose.", "Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS).\n To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS.\n Prospective, randomized, double-blind, placebo-controlled clinical study.\n Two tertiary-care hospitals in Duluth, Minnesota.\n Inpatient adults admitted for any reason (including AWS) judged to be at high risk for AWS.\n Inpatients who developed symptoms of AWS received symptom-triggered benzodiazepine treatment using lorazepam by standard protocol, and were randomized to receive baclofen 10 mg or placebo, 3 times per day, orally.\n AWS severity was assessed using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar); lorazepam dose was monitored.\n Seventy-nine subjects were enrolled. The 44 subjects who developed symptoms of AWS were randomized to baclofen or placebo. Thirty-one subjects (18 baclofen, 13 placebo) completed 72 hours of assessments, either entirely as inpatients or with outpatient follow-up. The need for high doses of benzodiazepines (20 mg or more of lorazepam over 72 hours) to control AWS was less likely in the baclofen treatment group (1 of 18) than in the placebo-treated group (7 of 13) (P = 0.004).\n We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety.\n Copyright © 2011 Society of Hospital Medicine.", "An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/ day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.", "Seeing as gamma-hydroxybutyrate (GHB) and benzodiazepines interact with the GABA-transmitter system, we investigated whether GHB can replace the conventional therapy, which uses benzodiazepines in the treatment of alcohol withdrawal syndrome in ICU settings.\n 42 chronic alcoholics were included in this prospective and randomized study. Following the development of alcohol withdrawal syndrome, the patients were randomly allocated to the GHB or to the flunitrazepam group. In addition to this, clonidine was administered in order to treat autonomic signs of withdrawal. In cases were hallucinations occurred, haloperidol was administered.\n There was no significant difference in the efficacy of treatment used in the duration of mechanical ventilation and intensive care unit stay between groups. The patients in the GHB-group required significantly higher dosages of haloperidol and significantly lower dosages of clonidine. 14 out of 21 patients from the GHB-group developed hypernatriaemia and 15 out of 21 developed a metabolic alkalosis.\n Symptoms of the autonomic nervous system were more effectively prevented by GHB as evident in the lower dosage requirement of clonidine. However, GHB may not sufficiently block the hyperactivity of the dopaminergic system or may have an hallucinogenic effect itself. This may be evident from the higher dosages of haloperidol which were necessary. Due to the latter fact, the administration of GHB cannot be recommended in all patients suffering from AWS in ICU settings.", "Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses." ]

[ "15297305", "11533321", "10645510", "16389536", "17403764", "12069673", "3200183", "12623317", "10790817", "12356708", "16708309", "11433046", "14568634", "10533946", "6350633", "15728141", "12032887", "11493132", "19811593", "10227321", "12183309", "16150741", "3974058", "14510254", "1917265", "9250230", "16126741", "12718461", "14563900", "15249449", "10437971", "10980182", "11783694", "14553868" ]

[ "Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial.", "A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children.", "An evaluation of statewide strategies to reduce antibiotic overuse.", "Changing antibiotics prescribing practices in health centers of Khartoum State, Sudan.", "Barriers to optimal antibiotic use for community-acquired pneumonia at hospitals: a qualitative study.", "Changes in antibiotic prescribing for children after a community-wide campaign.", "Changing antibiotic prescribing by educational marketing.", "Impact of a multidisciplinary approach to the control of antibiotic prescription in a general hospital.", "Pilot study for appropriate anti-infective community therapy. Effect of a guideline-based strategy to optimize use of antibiotics.", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice.", "Reducing antibiotic use in children: a randomized trial in 12 practices.", "An interrupted time series analysis of parenteral antibiotic use in Colombia.", "Influencing antibiotic prescribing in general practice: a trial of prescriber feedback and management guidelines.", "Improving antibiotic prescribing in office practice. A controlled trial of three educational methods.", "Improving compliance with hospital antibiotic guidelines: a time-series intervention analysis.", "Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: A controlled intervention trial in rural Alaska.", "Academic detailing to improve use of broad-spectrum antibiotics at an academic medical center.", "A RCT evaluating the effectiveness and cost-effectiveness of academic detailing versus postal prescribing feedback in changing GP antibiotic prescribing.", "Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults.", "Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat.", "Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes: cluster randomised controlled trial.", "Persistence of improvement in antibiotic prescribing in office practice.", "Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years.", "Experimental evaluation of the effects of drug information on antibiotic prescribing: a study in outpatient care in an area of Sri lanka.", "Antibiotic optimization. An evaluation of patient safety and economic outcomes.", "Pharmacy-implemented guidelines on switching from intravenous to oral antibiotics: an intervention study.", "Mailed prescriber feedback in addition to a clinical guideline has no impact: a randomised, controlled trial.", "Outcomes of an intervention to improve hospital antibiotic prescribing: interrupted time series with segmented regression analysis.", "Limited impact of a multicenter intervention to improve the quality and efficiency of pneumonia care.", "Effect of antibiotic order form guiding rational use of expensive drugs on cost containment.", "Primary care workshops can reduce and rationalize antibiotic prescribing.", "Control of nosocomial multiresistant Enterobacteriaceae using a temporary restrictive antibiotic agent policy.", "Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial." ]

[ "To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care.\n Randomised controlled trial.\n Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands.\n The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients. The control group did not receive any of these elements.\n Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction.\n 89 general practitioners completed the study (89%). At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively). After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%). Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%). Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention.\n A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients. Further research should focus on the sustainability and cost effectiveness of this intervention.", "Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance. The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities.\n A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians. Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations. Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998).\n The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region. The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region. Retail antibiotic sales declined in the intervention region but not in the control region. Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions.\n A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility.", "The rapid increase of antibiotic resistance poses a significant threat to human health. Overuse of antibiotics has been linked to rates of antibiotic resistance. This study assessed the utility of two common interventions--1) practice profiling and feedback and 2) patient education materials--implemented to decrease antibiotic prescribing for pediatric upper respiratory infections (URIs).\n Based on Medicaid regions in Kentucky, primary care physicians managing pediatric respiratory infections in Medicaid were randomized into four groups. Groups received either 1) performance feedback only, 2) patient education materials only, 3) both feedback and education materials, or 4) no intervention. Participating physicians had their antibiotic prescribing assessed for the period of July 1, 1996, to November 30, 1997, with an intervention in June 1997. The study included 216 physicians and 124,092 episodes of care.\n All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods. Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group. Physicians did not change their coding of illness to justify antibiotics after the intervention, and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs.\n These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing. Antibiotic prescribing for viral respiratory infections continues to increase, suggesting concomitant increases in antibiotic resistance.", "A major problem with inappropriate use of antibiotics is the emergence of resistance. Thus, cost-effective interventional strategies are required to improve their use. This study aimed to evaluate the effect of multifaceted interventions on prescribing practices of antibiotics in health centers of Khartoum State, Sudan.\n Twenty health centers were randomly assigned to receive: (1) no intervention; (2) audit and feedback; (3) audit and feedback + seminar; or (4) audit and feedback + academic detailing. A total of 1,800 patient encounters, 30 from each health center, were randomly collected. The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice, dose and duration of therapy before the study and at 1 and 3 months post-intervention.\n In comparison to the control group, the prescriber targeted interventions involving audit and feedback, together with academic detailing (4), reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 (p<0.001) at 1 and 3 months post-intervention, respectively. In addition, the mean number of encounters with an inappropriate antibiotic with respect to diagnosis, doses and/ or duration of therapy was reduced by 5.3 and 5.9 (p<0.001) at 1 and 3 months post-intervention, respectively. For audit and feedback together with seminars (3) and for audit and feedback alone (2), the corresponding reductions were 5.3, 7.1, 4.4 and 5.1 (p<0.001) and 1.4, 2.8, 1.8 and 1.9 (p>0.05), respectively.\n Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State, Sudan, are alarmingly high. Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practices of antibiotics than audit and feedback alone.", "Physician adherence to key recommendations of guidelines for community-acquired pneumonia (CAP) is often not optimal. A better understanding of factors influencing optimal performance is needed to plan effective change.\n The authors used semistructured interviews with care providers in three Dutch medium-sized hospitals to qualitatively study and understand barriers to appropriate antibiotic use in patients with CAP. They discussed recommendations about the prescription of empirical antibiotic therapy that adheres to the guidelines, timely administration of antibiotics, adjusting antibiotic dosage to accommodate decreased renal function, switching and streamlining therapy, and blood and sputum culturing. The authors then classified the barriers each recommendation faced into categories using a conceptual framework (Cabana).\n Eighteen interviews were performed with residents and specialists in pulmonology and internal medicine, with medical microbiologists and a clinical pharmacist. Two additional multidisciplinary small group interviews which included nurses were performed. Each guideline recommendation elicited a different type of barrier. Regarding the choice of guideline-adherent empirical therapy, treating physicians said that they worried about patient outcome when prescribing narrow-spectrum antibiotic therapy. Regarding the timeliness of antibiotic administration, barriers such as conflicting guidelines and organisational factors (for example, delayed laboratory results, antibiotics not directly available, lack of time) were reported. Not streamlining therapy after culture results became available was thought to be due to the physicians' attitude of \"never change a winning team\".\n Efforts to improve the use of antibiotics for patients with CAP should consider the range of barriers that care providers face. Each recommendation meets its own barriers. Interventions to improve adherence should be tailored to these factors.", "Overuse of antibiotics has contributed to microbial resistance, compromising the treatment of bacterial infections. Very high levels (>50%) of antibiotic resistance among invasive Streptococcus pneumoniae have been documented in Knox County, Tennessee.\n To determine the effectiveness of a community-wide intervention aimed at reducing inappropriate antibiotic use among children.\n The Knox County Health Department led a multifaceted year-long campaign (May 1997 through April 1998) aimed at decreasing unnecessary antibiotic use among children. Tennessee's 3 other major urban counties (Shelby, Hamilton, and Davidson) did not conduct similar campaigns and served as controls. Evaluation included white and black children (aged <15 years) enrolled in Tennessee's Medicaid Managed Care Program in the 4 study counties, representing 36% of the study counties' children (464 200 person-years observed).\n Educational efforts were directed toward health care practitioners (primarily via peer leader presentations) and to the parents of young children and the public (primarily via printed materials).\n The intervention-attributable effect on antibiotic use, defined as the excess percentage change in oral antibiotic prescription rates in Knox County between the 12-month preintervention and postintervention periods, relative to that of control counties.\n Antibiotic prescription rates declined 19% and 8% among Knox County and control county children, respectively, yielding an 11% intervention-attributable decline (95% confidence interval, 8%-14%; P<.001). The intervention-attributable decrease in prescription rates was greatest among children aged 1 to less than 5 years (among white children, 8% [P<.001]; among black children, 18% [P<.001]).\n A community-wide educational intervention reduced antibiotic prescription levels among children in Knox County.", "A controlled cross-over study in 12 Victorian public hospitals was performed to examine the power of marketing techniques in influencing prescribing. The targeted prescribing behaviour was the use of antibiotic prophylaxis in surgery, and the criteria for judging the appropriateness of therapy were its duration and timing, as are detailed in the fourth edition of the booklet Antibiotic guidelines. The first intervention was mounted in 1985 in six hospitals (two metropolitan teaching hospitals, one suburban general hospital and three rural hospitals), and six matched hospitals acted as control hospitals. One year later, the intervention was mounted in the six hospitals that previously had been the control hospitals. The interventional campaign consisted of material that was similar to that which is used by the pharmaceutical industry, including an \"academic\" representative. Its effect was assessed by audits that were performed before and after the first interventional campaign and again, one year later, after the second interventional campaign. The proportion of antibiotic courses that were assessed as satisfactory in terms of duration increased significantly after the first campaign in the hospitals where the intervention was mounted. No significant changes in prescribing occurred in the control hospitals. In the hospitals which were control hospitals in 1985, and in which the intervention occurred in 1986, the proportion of antibiotic courses that were assessed as satisfactory also increased significantly after the interventional campaign. A fall-off in performance occurred during the 12 months after the campaign in the 1985-interventional hospitals. Calculated cost savings more than outweighed the costs of the campaign. We conclude that inappropriate prescribing behaviour in hospitals can be modified successfully by educational marketing techniques.", "We examined the impact of a rational antibiotic prescription programme based on a multidisciplinary consultative approach in a 600-bed hospital. The programme involved four measures: (1). drawing up of a local prescribing consensus with all prescribers; (2). a restricted prescriptions policy for the most expensive antibiotics; (3.assessment of the prescription of these antibiotics by regular audits; and (4). institutional training and information for prescribers. The impact of the programme was assessed by comparing actual prescriptions with the criteria of the local consensus, compliance with the restrictive prescription policy, changes in the average daily cost of antibiotic therapy per inpatient and changes in the local ecology of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae producing extended-spectrum beta-lactamases (EPESB) and ceftazidime-resistant Pseudomonas species (CRP). Using a participatory consensual approach, 182 reference recommendations were established (104 for adults, 78 for children), corresponding to 85% of the clinical settings encountered in the hospital. Six audits, conducted since June 1997, show that the rate of unjustified prescriptions first fell significantly (from 6 to 0%, P<0.001), then increased significantly (from 0 to 3%, P<0.05) before stabilizing at 3%. The cost of antimicrobials per inpatient day fell significantly (from US dollars 13.8 in 1997 to US dollars 11 in 2000, P<0.001). The prevalence of MRSA and CRP remained stable, while that of EPESB fell significantly (P<0.001). This multidisciplinary consultative approach thus reduced antibiotic costs, contributed to infection control, and improved the quality of antibiotic prescription.", "To determine whether a community-wide, multi-intervention educational strategy (CoMPLI model) could enhance adoption of clinical guidelines and improve the use of antibiotics.\n Before-after trial using baseline and study periods with a control group.\n A small community in central Ontario.\n Health professionals, the general public, and the pharmaceutical industry.\n The educational strategy (CoMPLI), carried out during 6 winter months, consisted of continuing medical education sessions for health professionals and pharmaceutical representatives and a parallel public education campaign that included town hall meetings and pamphlets distributed by local pharmacists. The two main messages were: do not use antibiotics for viral respiratory infections, and use drugs recommended in the publication, Anti-infective Guidelines for Community-Acquired Infections.\n Total number of antibiotic claims and adjusted odds ratios (OR) were used to measure the likelihood of physicians prescribing first- or second-line agents compared with the previous year and compared with control physicians.\n Claims in the study community decreased by nearly 10% during the 6-month study period compared with the baseline period from the previous year. Study physicians were 29% less likely (OR-1 = 0.71, range 0.67 to 0.76) to prescribe second-line antibiotics during the study period than physicians in the rest of the province.\n Physicians participating in the pilot study were more likely to follow drug recommendations outlined in published guidelines.", "Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.", "A cluster-randomised controlled trial in general practice\n Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication.\n We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days.\n The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70).\n In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high.", "To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old.\n Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed.\n The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses.\n A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.", "A University-based hospital in Bogotá, Colombia, developed and implemented an educational intervention to complement a new structured antibiotic order form. This intervention was performed after assessing the appropriateness of the observed antibiotic prescribing practices using a quasi-experimental study. An application of interrupted time series intervention analysis was conducted in three antibiotic groups (aminoglycosides, cephradine/cephalothin, and ceftazidime/cefotaxime) and their hospital weekly rate of incorrect prescriptions before and after the intervention. A fourth time series was defined on prophylactic antibiotic use in elective surgery. Preintervention models were used in the postintervention series to test for pre-post series level differences. An abrupt constant change was significant in the first, third, and fourth time series indicating a 47, 7.3, and 20% reduction of incorrect prescriptions after the intervention. We conclude that a structured antibiotic order form, coupled with graphic and educational interventions can improve antibiotic use in a university hospital.", "The extent of use of antibiotics to treat upper respiratory infections in general practice is an area for concern due to the increasing problem of bacterial resistance. Effective educational strategies to promote rational prescribing are needed.\n We aimed to examine the effectiveness of prescriber feedback and management guidelines in reducing antibiotics prescribing by GP trainees for undifferentiated upper respiratory tract infection, and in improving the choice of antibiotic for tonsillitis/streptococcal pharyngitis. The research tested a stepwise approach to targeting educational input to high prescribers.\n General Practice trainees in New South Wales (n = 157) were randomly allocated to a treatment group (n = 78) which received an education intervention on antibiotic use, or to a control group (n = 79) which received an intervention on an unrelated topic. Trainees completed three practice activity surveys, each of 110 consecutive patient encounters, with 6-month intervals between surveys. Prescriber feedback and management guidelines on use of antibiotics for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis were delivered in a written form between surveys 1 and 2. An educational outreach visit to high prescribers occurred between surveys 2 and 3. Outcome measures were the rate of antibiotic prescribing for all indications, for URTI and prescribing of select antibiotics for tonsillitis/streptococcal pharyngitis.\n Antibiotic prescribing by the intervention group declined over three occasions from 25.0 to 23.3 to 19.7 per 100 URTI problems, while the control group increased from 22.0 to 25.0 to 31.7 per 100 URTI problems (P = 0.002). Prescribing in agreement with accepted guidelines for tonsillitis/streptococcal pharyngitis increased over time in the intervention group from 55.6 to 69.8 to 73.0 per 100 problems, but decreased in the control group from 59.6 to 57.5 to 58.5 (P = 0.05).\n Prescriber feedback and management guidelines were shown to influence antibiotic prescribing for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis. This study provides a model for targeting educational input to those prescribers who most need to change their behaviour.", "We conducted a statewide controlled trial of three methods to improve antibiotic prescribing in office practice: a mailed brochure, a drug educator visit, and a physician visit. Educational topics were three antibiotics contraindicated for office practice and oral cephalosporins. Medicaid prescribing data were used to select donors who needed education. The effect of the methods was evaluated by comparing the change in prescribing (the year before the intervention v the year after the intervention) for the doctors receiving education with the prescribing of comparable doctors chosen as controls. The mailed brochure had no detectable effect, and the drug educator had only a modest effect. The physician visits produced strong attributable reductions in prescribing of both drug classes. For the contraindicated antibiotics, the reductions were 18% in number of doctors prescribing, 44% in number of patients per doctor receiving these drugs, and 54% in number of prescriptions written per doctor. For the oral cephalosporins, both number of patients and number of prescriptions per doctor were reduced by 21%. Doctors responded equally well to recommendations designed to improve the quality of care and to reduce the cost of care.", "This study investigated the impact of a combined intervention strategy to improve antimicrobial prescribing at University Hospital Groningen. For the intervention, the antimicrobial treatment guidelines were updated and disseminated in paperback and electronic format. The credibility of the guidelines was improved by consultation with users. In a second phase, academic detailing (AD) was used to improve specific areas of low compliance with the guidelines. Materials and methods: Prescribing data were prospectively collected for 2869 patients receiving 7471 prescriptions for an antimicrobial for an infection covered by the guidelines between July 2001 and September 2003. After collection of baseline data, the guidelines were actively disseminated in February 2002. Next, after a 5 month interval, a second intervention, i.e. an AD approach, addressed suboptimal prescribing of ciprofloxacin and co-amoxiclav. Segmented regression analysis was used to analyse the interrupted time-series data.\n At baseline, compliance with the drug choice guidelines was 67%. The first intervention showed a significant change in the level of compliance of +15.5% (95% CI: 8%; 23%). AD did not lead to statistically significant additional changes in already high levels +12.5% (95% CI:-3%; 28%) of compliance. Post-intervention compliance was stable at 86%.\n Updating the guidelines in close collaboration with the specialists involved followed by active dissemination proved to be an efficient way to improve compliance with guideline recommendations. An 86% compliance level was achieved in this study without compulsory measures. A ceiling effect may have limited the added value of AD.", "From 1998 to 2000, 13 rural Alaskan villages (population, 3326) were surveyed annually by nasopharyngeal cultures for Streptococcus pneumoniae carriage. Data regarding antibiotic use for the entire population was abstracted from clinic records. In 1999, education of medical providers and the community about appropriate antibiotic use began in 4 villages; this program was expanded to include all villages in 2000. Antibiotic courses per person decreased by 31% in the initial intervention villages and by 35% in the remaining villages after education (P<.01 for each). Samples were obtained for culture from a mean of 31% of the population each year; 31% carried pneumococcus. No sustained decrease in carriage of penicillin-nonsusceptible strains was observed. When linear regression was used, serotype accounted for 81% of the variance in pneumococcal minimum inhibitory concentrations after the intervention, compared with 7% for antibiotic use. This suggests that reducing the carriage of serotypes associated with antibiotic resistance by use of pneumococcal conjugate vaccines may have a greater short-term impact than does decreasing antibiotic use.", "Antibiotic misuse is common and costly and may promote antibiotic resistance. We tested the efficacy of a targeted one-on-one educational program (\"academic detailing\") designed to improve the appropriateness of broad-spectrum antibiotic use.\n A randomized controlled trial was conducted in a large US teaching hospital. During an 18-week study period, 17 general medical, oncology, and cardiology services either received academic detailing or did not. The intervention was prompted by an order for either levofloxacin or ceftazidime that led to a computer-based review of data for that patient. Orders for the 2 target antibiotics deemed unnecessary by a priori criteria were included in the study. The primary outcome examined was the number of days that unnecessary levofloxacin or ceftazidime was administered in intervention and control groups.\n Before the trial, intervention and control services had similar prescribing patterns for the target antibiotics; the drugs were used for similar indications throughout the study period. During the intervention, there was a reduction of 37% in days of unnecessary levofloxacin or ceftazidime use per 2-week interval on services randomized to the educational intervention vs control services (P< .001). In multivariable analyses controlling for baseline prescribing and study interval, the rate of unnecessary use of the 2 target antibiotics was reduced by 41% on the intervention services compared with controls (95% confidence interval, 44%-78%; P< .001). Length of stay, intensive care unit transfers, readmission rates, and in-hospital death rates were similar in both groups (P> or =.10 for all).\n Targeted one-on-one education is a practical, effective, and safe method for reducing excessive broad-spectrum antibiotic use.", "The aim of this study is to evaluate the effectiveness of academic detailing (AD) plus postal prescribing feedback versus postal prescribing feedback alone in reducing: (i) the overall rate of antibiotic; and (ii) proportion of second-line antibiotic prescribing. In addition, the cost-effectiveness of an outreach prescriber adviser service versus a postal prescribing feedback service was evaluated.\n Volunteer general practitioner practices (n = 98) were randomized to receive prescribing feedback via postal bulletin (PB) (n = 50) or academic detailing plus postal bulletin (AD) (n = 48). Data analysis was based on the HSE-primary care reimbursement service (HSE-PCRS) prescribing database. Regression (beta) coefficients, indicating proportion change in prescribing per month, and 95% confidence intervals (CIs) are presented. The cost-effectiveness ratio was calculated from the total cost of the intervention divided by percentage change in antibiotic prescribing in AD versus PB group.\n Immediately post intervention PB (beta = -0.02, 95% CI -0.04, -0.001) and AD (beta = -0.02, 95% CI -0.03, -0.001) practices significantly decreased overall antibiotic prescribing. Second-line antibiotic prescribing was also significantly decreased by 2-3% in both groups. However, there were no significant differences in antibiotic prescribing between the randomized groups in the immediate or long-term post-intervention period. In the cost-effectiveness analysis a postal prescribing feedback service would cost euro 88 per percentage change in prescribing practice compared with euro 778 for a prescriber adviser service.\n Prescribing feedback significantly reduced overall and second-line antibiotic prescribing, but academic detailing was not significantly more effective than postal bulletin in changing antibiotic prescribing practice.", "The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due, in part, to the excessive use of antibiotics for acute respiratory tract infections.\n To decrease total antibiotic use for uncomplicated acute bronchitis in adults.\n Prospective, nonrandomized controlled trial, including baseline (November 1996-February 1997) and study (November 1997-February 1998) periods.\n Four selected primary care practices belonging to a group-model health maintenance organization in the Denver, Colo, metropolitan area.\n Consecutive adults diagnosed as having uncomplicated acute bronchitis. A total of 2462 adults were included at baseline and 2027 adults were included in the study. Clinicians included 56 physicians, 28 physician assistants or nurse practitioners, and 9 registered nurses.\n The full intervention site received household and office-based patient educational materials, as well as a clinician intervention consisting of education, practice-profiling, and academic detailing. A limited intervention site received only office-based educational materials, and control sites provided usual care.\n Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods.\n Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period. During the study period, there was a substantial decline in antibiotic prescription rates at the full intervention site (from 74% to 48% [P = .003]), but not at the control and limited intervention sites (78% to 76% [P = .81] and 82% to 77% [P = .68], respectively). Compared with control sites, changes in nonantibiotic prescriptions (inhaled bronchodilators, cough suppressants, and analgesics) were not significantly different for intervention sites. Return office visits (within 30 days of the incident visit) for bronchitis or pneumonia did not change significantly for any of the sites.\n Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions.", "To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat.\n Unblinded, cluster randomised pretest-post-test trial.\n 142 general practices in Norway.\n 72 practices received interventions to implement guidelines for urinary tract infection and 70 practices received interventions to implement guidelines for sore throat, serving as controls for each other. 59 practices in the urinary tract infection group and 61 practices in the sore throat group completed the study. Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection.\n Interventions were developed to overcome identified barriers to implementing the guidelines. The main components of the tailored interventions were patient educational material, computer based decision support and reminders, an increase in the fee for telephone consultations, and interactive courses for general practitioners and practice assistants.\n Changes in rates of use of antibiotics, laboratory tests, and telephone consultations. Results: Patients in the sore throat group were 3% less likely to receive antibiotics after the intervention. Women with symptoms of urinary tract infection in the intervention group were 5.1% less likely to have a laboratory test ordered. No significant differences were found between the groups for the other outcomes. Large variation was found across the included practices in the rates of antibiotic prescription, use of laboratory tests and telephone consultations, and in the extent of change for all three outcome measures.\n Passively delivered, complex interventions targeted at identified barriers to change had little effect in changing practice.", "To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes.\n Cluster randomised controlled trial.\n 24 nursing homes in Ontario, Canada, and Idaho, United States.\n 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care. Outcomes were measured in 4217 residents.\n Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach--small group interactive sessions for nurses, videotapes, written material, outreach visits, and one on one interviews with physicians.\n Number of antimicrobials prescribed for suspected urinary tract infections, total use of antimicrobials, admissions to hospital, and deaths.\n Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference -0.49, 95% confidence intervals -0.93 to -0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference -9.6%, -16.9% to -2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighted mean difference -0.37, -1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms.\n A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes.", "We evaluated persistence of the prescribing improvement seen in a previous statewide controlled trial, which measured improvement in the prescribing of contraindicated antibiotics and oral cephalosporins in the year after an educational intervention. Doctors visited by physician-counselors substantially improved their prescribing of both classes of drugs. The beneficial effect of the physician-counselors persisted throughout year 2, with attributable reductions in prescribing of 30% and savings of $950 for each doctor visited. The marked and lasting improvement in prescribing produced by the physician-counselors suggests using this model to develop ongoing programs to improve prescribing.", "To evaluate the impact of an interventional multidisciplinary antibiotic management program on expenditures for antibiotics and on the incidence of nosocomial infections caused by Clostridium difficile and antibiotic-resistant pathogens during 7 years.\n Prospective study with comparison with preintervention trends.\n University-affiliated teaching hospital.\n All adult inpatients.\n A multidisciplinary antibiotic management program to minimize the inappropriate use of third-generation cephalosporins was implemented in 1991. Its impact was evaluated prospectively. The incidence of nosocomial C. difficile and resistant Enterobacteriaceae infections as well as the rate of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of National Nosocomial Infections Surveillance System hospitals of similar size.\n Following implementation of the program, there was a 22% decrease in the use of parenteral broad-spectrum antibiotics (P < .0001) despite a 15% increase in acuity of patient care during the following 7 years. Concomitantly, there was a significant (P = .002) decrease in nosocomial infections caused by C. difficile and a significant (P = .02) decrease in nosocomial infections caused by resistant Enterobacteriaceae. The program also appeared to have a favorable impact on VRE rates without a sustained impact on MRSA rates.\n These results suggest that an ongoing multidisciplinary antibiotic management program may have a sustained beneficial impact on both expenditures for antibiotics and the incidence of nosocomial infection by C. difficile and resistant bacterial pathogens.", "The intervention level of epidemiology is useful for studying effects in health systems research. Due to practical and ethical reasons, it is often difficult to apply experimental methods such as classical randomized clinical trials in the field. However with alternative approaches such as 'randomization by group' some of these problems can be overcome. Drug information has since long been considered as an instrument to influence physicians, however evaluation of its effects is a new field of research. In the present study the impact of drug information on prescribing behaviour was evaluated in an outpatient setting in Sri Lanka. The study included 15 state health institutions (45 prescribers) with a common drug formulary. Groups of prescribers were randomized into two interventions; newsletters and newsletters reinforced by a group seminar, and one control group. The target topic was 'rational prescribing of antibiotics'. Some 18,766 randomly selected outpatient drug prescriptions were studied. Antibiotics (and sulphonamides) were prescribed to 33.2% of the patients. An overall trend towards a decrease in proportion of patients prescribed antibiotics in the two intervention groups was seen, although the difference was not significant (p greater than 0.05) compared to the control group. This is similar to the effect of written information on prescribing in other studies. A mean difference of -7.4% in written, -7.3% in written + seminar and -0.4% in the control group was shown. The general antibiotic prescribing pattern did not change in any of the three groups. Penicillin was the most commonly prescribed antibiotic and tetracycline was only rarely prescribed to children. This experiment indicates the feasibility of drug information intervention studies in developing countries.(ABSTRACT TRUNCATED AT 250 WORDS)", "Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study.\n Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database.\n Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11).\n This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense.", "A high proportion of medical in-patients in the UK receive intravenous (IV) antibiotic therapy. This may be inappropriate in non-severe infections, or unnecessarily prolonged.\n To assess the impact of guideline implementation on IV antibiotic prescribing in medical admissions to a general hospital.\n Observational intervention study.\n Data relating to infection and antibiotic therapy were collected for 4 weeks pre-intervention (group 1) and 4 weeks post intervention (group 2). Six months later, data were collected for a further 4 weeks following a second intervention (group 3). Interventions consisted of pharmacy-led implementation of guidelines incorporating criteria for IV therapy and switching to the oral route. The second intervention also included pharmacy-initiated feedback on prescribing. The main outcome measures were IV antibiotic duration, and appropriateness of the IV route and switching.\n Of 2365 admissions, 757 (32%) had 806 treated episodes. IV therapy was used in 40%, 46% and 36% (groups 1, 2 and 3, respectively) and was appropriate in 92% vs. 100% (group 1 vs. 2). In groups 2 and 3, oral switch timing was appropriate in 90% and 88%, vs. 17% in group 1 (p < 0.001). Between groups 1 and 2, median duration of IV therapy was reduced from 3 to 2 days (p = 0.01). More patients in group 2 received appropriate exclusively IV therapy (65% vs. 96%, p < 0.01). Duration of stay in IV-treated patients reduced from 13 to 10 days in groups 2 and 3 (p = 0.047). IV antibiotic expenditure reduced by 13% per patient admitted between groups 1 and 2.\n Pharmacy-led introduction of antibiotic guidelines appears to result in clinically appropriate reductions in IV therapy.", "To evaluate the impact of feedback on the prescribing of antibiotics supplementary to clinical guidelines in the treatment of respiratory tract infections.\n Randomised, controlled trial with GPs allocated to one of two groups. The first group received clinical guidelines on the treatment of respiratory tract infections plus postal feedback with aggregated data on their prescribing patterns for antibiotics. The second group served as controls for the first group and received the guidelines only.\n 299 GPs representing 181 practices with 455,843 listed patients in the County of Funen, Denmark.\n Effects on GP prescribing patterns were measured by means of a prescription database and followed for a period of 2 years with 2 outcome measures: 1) the antibiotic prescription rate and 2) the fraction of prescriptions for narrow-spectrum antibiotics.\n The addition of feedback had no impact on GP prescribing patterns.\n Postal disseminated prescriber feedback in addition to a clinical guideline on the diagnosis and treatment of respiratory tract infections does not influence GP prescribing patterns. Interventions aimed at improving performance in general practice should go beyond just giving GPs information on whether they are living up to standards.", "To evaluate an intervention to reduce inappropriate use of key antibiotics with interrupted time series analysis.\n The intervention is a policy for appropriate use of Alert Antibiotics (carbapenems, glycopeptides, amphotericin, ciprofloxacin, linezolid, piperacillin-tazobactam and third-generation cephalosporins) implemented through concurrent, patient-specific feedback by clinical pharmacists. Statistical significance and effect size were calculated by segmented regression analysis of interrupted time series of drug use and cost for 2 years before and after the intervention started.\n Use of Alert Antibiotics increased before the intervention started but decreased steadily for 2 years thereafter. The changes in slope of the time series were 0.27 defined daily doses/100 bed-days per month (95% CI 0.19-0.34) and pound 1908 per month (95% CI pound 1238- pound 2578). The cost of development, dissemination and implementation of the intervention ( pound 20133) was well below the most conservative estimate of the reduction in cost ( pound 133296), which is the lower 95% CI of effect size assuming that cost would not have continued to increase without the intervention. However, if use had continued to increase, the difference between predicted and actual cost of Alert Antibiotics was pound 572448 (95% CI pound 435696- pound 709176) over the 24 months after the intervention started.\n Segmented regression analysis of pharmacy stock data is a simple, practical and robust method for measuring the impact of interventions to change prescribing. The Alert Antibiotic Monitoring intervention was associated with significant decreases in total use and cost in the 2 years after the programme was implemented. In our hospital, the value of the data far exceeded the cost of processing and analysis.", "To evaluate the impact of a multifactorial intervention to improve the quality, efficiency, and patient understanding of care for community-acquired pneumonia.\n Times series cohort study.\n Four academic health centers in the New York City metropolitan area.\n All consecutive adults hospitalized for pneumonia during a 5-month period before (n = 1,013) and after (n = 1,081) implementation of an inpatient quality improvement (QI) initiative.\n A multidisciplinary team of opinion leaders developed evidence-based treatment guidelines and critical pathways, conducted educational sessions with physicians, distributed pocket reminder cards, promoted standardized orders, and developed bilingual patient education materials.\n The average age was 71.4 years, and 44.1% of cases were low risk, 36.8% were moderate risk, and 19.2% were high risk. The preintervention and postintervention groups were well matched on age, sex, race, nursing home residence, pneumonia severity, initial presentation, and most major comorbidities. The intervention increased the use of guideline-recommended antimicrobial therapy from 78.1 to 83.4% (p = 0.003). There was also a borderline decrease in the proportion of patients being discharged prior to becoming clinically stable, from 27.0 to 23.5% (p = 0.06). However, there were no improvements in the other targeted indicators, including time to first dose of antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral antibiotics, timely discharge, length of stay, or patient education outcomes.\n This real-world QI program was able to improve modestly on some quality indicators, but not effect resource use or patient knowledge of their disease. Changing physician and organizational behavior in academic health centers will require the development and implementation of more intensive, system-oriented strategies.", "New injectable antimicrobial agents are generally costly and broad-spectrum. Overusage results in unnecessary economic loss and multi-drug resistant organisms. Effective strategies for decreasing costs without compromising patient care are required. This study aimed to evaluate the economic impact of a system using an antimicrobial order form to assist rational usage of expensive antimicrobial agents. The study was performed during 1988-1996 at a 900-bed, tertiary-care, medical school hospital in Bangkok. The target drugs were 3 costly, broad-spectrum antibacterial drugs, namely imipenem, vancomycin, and injectable ciprofloxacin. The restriction of these 3 drugs was started in 1992 and was extended to netilmicin and ceftazidime in 1995. A filled antimicrobial order form (AOF) was required by pharmacists before dispensing the drugs. The AOF guided the physicians to give explicit information about anatomic diagnosis, etiologic diagnosis, and suspected antimicrobial resistance patterns of the organisms. It also contained information about indications of the restricted drugs. The filled forms were audited daily during working days by the chairman of The Hospital Antibiotic Committee. Feedback was given to the prescribers by infectious disease specialists at least twice a week. The strategy was endorsed by the executive committee of the hospital. Impact of AOF without endorsement, audit and feedback, was evaluated in 1996. The expenditures of the drugs were adjusted to the average admitted patient-days per fiscal year of the study period. The system with endorsement was well accepted and could be maintained for 4 years. The adjusted expenditures per year of the 3 restricted antibiotics were 1.41-1.87 million baht less (22-29%) in 1992-1994 than the pre-intervention year 1991. The cost reduction of imipenem and injectable ciprofloxacin could also be maintained for 1995 but not vancomycin for which use increased. The costs of these 3 restricted drugs increased very sharply (69%) in 1996 when there was loss of endorsement and capacity to perform auditing and feed back by infectious disease specialists. The system did not work with ceftazidime which was commonly used for febrile neutropenia and nosocomial infections.", "We describe a controlled study comparing the effects on primary care prescribing in west Gloucestershire, UK, where antibiotic workshops were offered, with those in east Gloucestershire, where microbiology tutorials were given. The year-on-year changes in quantity and costs of antibiotics dispensed following general practice prescriptions were measured. There was no significant difference in the number of antibiotic items prescribed across the county, but the number of prescriptions for broad-spectrum agents (quinolones, cephalosporins and co-amoxiclav) declined by 15.4% in west Gloucestershire, compared with a 6.5% increase in east Gloucestershire (P: = 0.002). Use of narrow-spectrum antibiotics (penicillin V, trimethoprim and nitrofurantoin), whose use was encouraged, did not change in west Gloucestershire practices, but decreased by 12% in east Gloucestershire practices (P: = 0.003). There was increased use of clarithromycin and azithromycin in both groups of practices. Antibiotic workshops held in the primary care setting can rationalize antibiotic prescribing. This can reduce prescribing costs and selection pressure by broad-spectrum antimicrobial agents and, perhaps, go some way to reducing the development of resistance.", "An observational study on the epidemiology of multiresistant Enterobacteriaceae was conducted in the neurology and neurosurgery wards of a university hospital to determine the impact of hospital hygiene measures and an additional temporary restrictive antibiotic agent policy on the sudden rise in incidence of these bacteria. The incidence and prevalence of patients with multiresistant Enterobacteriaceae were assessed, and patient isolates were typed phenotypically and by random amplified polymorphic DNA analysis. All hospital hygiene measures implemented were recorded, and the influence of the restrictive policy on antibiotic use was analyzed. This policy consisted of a prior authorization requirement and the withdrawal of all antibiotics with a possible selective pressure on multiresistant strains (gentamicin, tobramycin, quinolones, cotrimoxazole, broad-spectrum penicillins, and cephalosporins). This ban left only carbapenems and amikacin for treatment. Typing showed that 17 of the 61 (28%) patients involved were infected or colonized with a single multiresistant strain of Klebsiella oxytoca, for which an environmental source was identified. The isolates recovered from the other patients comprised eight different species, and subsequent genotyping yielded a great variety of strains. The increased incidence could not be controlled with hospital hygiene measures alone. Only after implementation of the restrictive antibiotic policy did the epidemic strain vanish and the endemic incidence of multiresistant Enterobacteriaceae decrease to <50% of the level before intervention. In the years since, the incidence has remained at this low level, and the antibiotic costs have decreased to a level lower than before intervention.", "Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.\n In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.\n Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.\n The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes." ]

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[ "Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: the RealTrend study.", "Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study.", "Patient-reported outcomes for an integrated real-time continuous glucose monitoring/insulin pump system.", "Continuous glucose monitoring-guided insulin adjustment in children and adolescents on near-physiological insulin regimens: a randomized controlled trial.", "Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment.", "Use of the Continuous Glucose Monitoring System to guide therapy in patients with insulin-treated diabetes: a randomized controlled trial.", "Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes.", "Continuous subcutaneous glucose monitoring improved metabolic control in pediatric patients with type 1 diabetes: a controlled crossover study.", "Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.", "Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial.", "The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better than frequent capillary glucose measurements for improving metabolic control.", "Continuous subcutaneous glucose monitoring in children with type 1 diabetes mellitus: a single-blind, randomized, controlled trial.", "Results of a randomised controlled cross-over trial on the effect of continuous subcutaneous glucose monitoring (CGMS) on glycaemic control in children and adolescents with type 1 diabetes.", "Continuous subcutaneous glucose monitoring in children with type 1 diabetes.", "Multicentre, randomised, controlled study of the impact of continuous sub-cutaneous glucose monitoring (GlucoDay) on glycaemic control in type 1 and type 2 diabetes patients.", "Quality-of-life measures in children and adults with type 1 diabetes: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring randomized trial.", "Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion.", "Short-term effects on patient satisfaction of continuous glucose monitoring with the GlucoDay with real-time and retrospective access to glucose values: a crossover study.", "Use of a blood glucose monitoring manual to enhance monitoring adherence in adults with diabetes: a randomized controlled trial." ]

[ "To compare the improvements in glycemic control associated with transitioning to insulin pump therapy in patients using continuous glucose monitoring versus standard blood glucose self-monitoring.\n The RealTrend study was a 6-month, randomized, parallel-group, two-arm, open-label study of 132 adults and children with uncontrolled type 1 diabetes (A1C >or=8%) being treated with multiple daily injections. One group was fitted with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated continuous subcutaneous glucose monitoring (CGM) capability, with instructions to wear CGM sensors at least 70% of the time. Conventional insulin pump therapy was initiated in the other group (continuous subcutaneous insulin infusion [CSII] group). Outcome measures included A1C and glycemic variability.\n A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group -0.81 +/- 1.09%, P < 0.001; CSII group -0.57 +/- 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear >or=70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group -0.96 +/- 0.93%, P < 0.001; CSII group -0.55 +/- 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia.\n CGM-enabled insulin pump therapy improves glycemia more than conventional pump therapy during the first 6 months of pump use in patients who wear CGM sensors at least 70% of the time.", "The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems.\n This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated.\n A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%) in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P=0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P=0.04).\n A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.", "A 16-week, two-site study evaluated outcomes for a new device (the Paradigm 722 System, Medtronic MiniMed, Northridge, CA) that combines a \"smart\" continuous subcutaneous insulin infusion (CSII) pump with real-time (RT) continuous glucose monitoring (CGM) and CareLinktrade mark data management software (DMS).\n CSII-naive adults with type 1 diabetes in suboptimal control (mean glycosylated hemoglobin [A1C] = 8.6%) were randomized to the control arm, consisting of multiple daily injections (MDI) and self-monitoring of blood glucose (SMBG), or the study arm (CSII with RT-CGM as an adjunct to SMBG). Participants (n = 28) completed the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and the parallel Blood Glucose (BG) Monitoring System Rating Questionnaire (BGMSRQ) at study start and end. Participants in the study arm (n = 14) also completed newly developed User Acceptance Questionnaires (UAQs) for CSII, RT-CGM, and DMS at study end.\n A1C reduction from study start to end was significant (P < 0.05) in both arms (-1.7% for study arm;-1.0% for control arm); there was no significant change in weight in either arm. The IDSRQ showed significantly (P < 0.05) greater benefit for the study arm in convenience, acceptability of BG monitoring requirements, BG control efficacy, diabetes worries, and interpersonal hassles, as well as higher overall satisfaction/preference. The BGMSRQ showed significantly (P < 0.05) greater benefit for the study arm in the BG monitoring system's ability to help manage glycemic control and less interest in changing to another BG monitoring system. The Study Arm UAQs showed positive ratings of system features.\n Several patient-reported outcomes were significantly more positive in the study arm than the control arm; none was significantly more positive in the control arm. The features of the integrated RT-CGM/CSII system were frequently used and highly rated by participants, with high user satisfaction.", "This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine.\n Pediatric subjects were recruited if they had an HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group.\n There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (-0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia.\n CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting.", "The value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined.\n A total of 160 children (aged 1-16 years, mean ± SD: 8.7 ± 4.4 years; 47.5% girls) were randomised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements. The primary outcome was the level of HbA(1c) after 12 months. Other analyses included fasting C-peptide, glycaemic variability, sensor usage, adverse events, children's health-related quality of life and parent's wellbeing.\n HbA(1c) was not significantly different between the two groups, but patients with regular sensor use had lower values (mean 7.1%, 95% CI 6.8-7.4%) compared with the combined group with no or low sensor usage (mean 7.6%, 95% CI 7.3-7.9%; p=0.032). At 12 months, glycaemic variability was lower in the sensor group (mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7; p=0.037). Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients (0.25 ± 0.12 nmol/l) compared with those treated with insulin pump alone (0.19 ± 0.07 nmol/l; p=0.033). Severe hypoglycaemia was reported only in the group without sensors (four episodes).\n Sensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children, although regular sensor use is a prerequisite for improved glycaemic control.\n ISRCTN.org ISRCTN05450731\n Medtronic International Trading Sàrl, Tolochenaz, Switzerland.", "To show improved glycemic control in patients with insulin-treated diabetes after adjustments to the diabetes management plan based on either continuous glucose monitoring using the Continuous Glucose Monitoring System (CGMS) or frequent self-monitoring of blood glucose (SMBG) using a home blood glucose meter.\n From January to September 2000, patients aged 19 to 76 years with insulin-treated diabetes were assigned to insulin therapy adjustments based on either CGMS or SMBG values. At the end of the study, patients in both groups used the CGMS for 3 days; these values were used to calculate measures of hypoglycemia. Repeated-measures analysis of variance with post hoc comparisons were used to test differences in hemoglobin A1c levels and hypoglycemia between the 2 study groups.\n A total of 128 patients were enrolled in the study. Nineteen discontinued study participation, leaving 51 in the CGMS group and 58 in the SMBG group. No significant differences were noted in demographics or baseline characteristics between the 2 groups. There were no significant differences in hemoglobin A1c levels between the CGMS group and the SMBG group at baseline (9.1% +/- 1.1% vs 9.0% +/- 1.0%, P = .70), and both groups showed statistically significant (P < .001) and similar (P = .95) improvement in hemoglobin A1c levels after 12 weeks of study. However, the CGMS group had a significantly shorter duration of hypoglycemia (sensor glucose, < or = 60 mg/dL) at week 12 of the study (49.4 +/- 40.8 vs 81.0 +/- 61.1 minutes per event, P = .009).\n Use of the CGMS to guide therapy adjustments in patients with insulin-treated diabetes reduces the duration of hypoglycemia compared with therapy adjustments guided by SMBG values alone.", "Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors.\n In this 1-year, multicenter, randomized, controlled trial, we compared the efficacy of sensor-augmented pump therapy (pump therapy) with that of a regimen of multiple daily insulin injections (injection therapy) in 485 patients (329 adults and 156 children) with inadequately controlled type 1 diabetes. Patients received recombinant insulin analogues and were supervised by expert clinical teams. The primary end point was the change from the baseline glycated hemoglobin level.\n At 1 year, the baseline mean glycated hemoglobin level (8.3% in the two study groups) had decreased to 7.5% in the pump-therapy group, as compared with 8.1% in the injection-therapy group (P<0.001). The proportion of patients who reached the glycated hemoglobin target (<7%) was greater in the pump-therapy group than in the injection-therapy group. The rate of severe hypoglycemia in the pump-therapy group (13.31 cases per 100 person-years) did not differ significantly from that in the injection-therapy group (13.48 per 100 person-years, P=0.58). There was no significant weight gain in either group.\n In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (Funded by Medtronic and others; ClinicalTrials.gov number, NCT00417989.)\n 2010 Massachusetts Medical Society", "To improve metabolic control and prevent complications, both acute and late, we need to adjust treatment on the basis of the blood glucose (BG) profile, as not even the most active BG self-monitoring gives sufficient information.\n We have used Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA) in a controlled crossover study including 27 diabetic patients aged 12.5 +/- 3.3 (mean; standard deviation; range: 5-19) years. All patients were treated with intensive insulin therapy, 14 with multiple injections, and 13 with pumps. The patients were randomized into an open or blind study arm. Both arms wore the CGMS sensor for 3 days every 2 weeks. CGMS profiles were used in the open study arm to adjust insulin therapy at follow-up visits every 6 weeks. Both the patients and the diabetes team were masked to the CGMS profiles in the blinded arm, and insulin therapy adjustments were based solely on 7-point BG profiles performed by the patients. At 3 months the 2 study arms were crossed over.\n Despite initial problems with a device new to both patients and the diabetes team, hemoglobin A(1)C decreased significantly in the open arm (from 7.70%-7.31%) but not in the blind arm (7.75%-7.65%). A total of 26/27 patients experienced daytime low subcutaneous glucose (<3.0 mmol/L;.8 episodes/day; duration 58 +/- 29 minutes; 5.5% of total time), and 27/27 patients had at least 1 nocturnal episode of low subcutaneous glucose (.4 episodes/night; duration 132 +/- 81 minutes; 10.1% of total time).\n Use of CGMS facilitated an improved treatment, and patients received new insight and increased motivation. In this study, we found CGMS to be a useful tool for education and improving metabolic control.", "To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes.\n In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed.\n The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group.\n Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.\n © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.", "The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy.\n An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability.\n Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred.\n Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable.\n ACTRN12606000049572", "To evaluate whether the continuous glucose monitoring system (CGMS; MiniMed, Sylmar, CA) is useful for investigating the incidence of unrecognized hypoglycemias in type 1 and type 2 diabetic patients and for improving metabolic control in type 1 diabetic patients.\n A total of 70 diabetic subjects (40 type 1 and 30 type 2 subjects) were monitored using the CGMS. The number of unrecognized hypoglycemias was registered. Furthermore, the 40 type 1 diabetic patients whose treatment was modified in accordance with the information obtained from the CGMS were compared with a control group of 35 different type 1 diabetic patients using intensive capillary glucose measurements. HbA(1c) levels were measured before the monitoring period and 3 months later.\n The CGMS detected unrecognized hypoglycemias in 62.5% of the type 1 diabetic patients and in 46.6% of the type 2 diabetic patients. We found that 73.7% of all events occurred at night. HbA(1c) concentrations decreased significantly in both the group of type 1 diabetic subjects monitored with the CGMS (from 8.3 +/- 1.6 to 7.5 +/- 1.2%, P < 0.01) and the control group (from 8.0 +/- 1.4 to 7.5 +/- 0.8%, P < 0.01). The greatest reduction was observed in the subgroup of patients who started continuous subcutaneous insulin infusion therapy, both in the CGMS-monitored and control groups (from 9.4 +/- 2 to 7.2 +/- 1.4% and from 8.1 +/- 1.8 to 7.1 +/- 0.6%, respectively).\n The CGMS is useful for detecting unrecognized hypoglycemias in type 1 and type 2 diabetic subjects; however, it is not better than standard capillary glucose measurements for improving metabolic control of type 1 diabetic subjects, regardless of the therapeutic regimen.", "Tight glycemic control delays the long-term complications of type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5 min, and its accuracy and reliability has been established in adults. However, there are limited data on its efficacy and safety in children. The purpose of this study was to determine if CGMS use improves metabolic control in children with T1DM.\n Twenty-seven children (12 male) with T1DM participated in this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7 (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n = 18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0, 2, and 4 months. Adjustments in therapy for the intervention group were based on both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6 months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70)) were compared between groups.\n At study entry, HbA1c levels were similar in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%, respectively; p = 0.12) but were significantly lower in the intervention group compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/- 0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the intervention group was statistically significant (p = 0.03), whereas the decrease in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the differences in HbA1c(Delta1-4) between groups did not reach statistical significance (p = 0.13). There was no statistically significant difference in AUC(<70) between study groups (p = 0.18).\n CGMS use may improve metabolic control in children with T1DM without increasing the risk for hypoglycemia.", "To study the feasibility and the influence on glycaemic control of continuous glucose monitoring (CGMS) in young patients with type 1 diabetes.\n A double-blinded, cross-over study was performed in 30 children (median age 11.1 years [range: 2.3 - 16.3], diabetes duration 2.1 years [0.2 - 7.1]). Patients were randomised into an open (A) or blind study arm (B). Both groups performed standardised self-monitoring blood glucose (SMBG) and received CGMS at the beginning of the study, at 3 and 6 months, each. In the blinded arm, patients and investigator were concealed from CGMS data. After 3 months, open and blinded study arms crossed over. Average glucose values and area under the glucose curve (AUC) per 24 h, above 180 and below 60 mg/dl were calculated from CGMS. Haemoglobin A1c (HbA1c) was measured at each study point.\n Despite comparable clinical characteristics between the 15 patients of each arm, mean HbA1c was slightly lower in arm A than in B at baseline (7.8 +/- 1.2 % vs. 8.4 +/- 1.1 %, p = 0.148), at 3 months (7.8 +/- 1.1 % vs. 8.3 +/- 1.1 %, p = 0.233), and significantly lower at 6 months (7.6 +/- 1.1 % vs. 8.5 +/- 0.9 %, p = 0.026). However, no significant change of HbA1c occurred within each arm (A, p = 0.183 and B, p = 0.823), irrespectively whether CGMS data were blinded or not. Likewise, mean glucose and hyper- or hypoglycaemia values did not change significantly.\n In this setting, CGMS did not decisively influence glycaemic control of a total study cohort. More frequent use of CGMS at shorter intervals in single patients with hyper- or hypoglycaemic problems may be of greater value than SMBG.", "To determine whether the use of continuous subcutaneous glucose monitoring will help in detecting unrecognized nocturnal hypoglycemia and in lowering hemoglobin A1c (HbA1c) levels (without increasing the risk for severe hypoglycemia) in children with type 1 diabetes.\n Eleven children with type 1 diabetes and HbA1c values consistently >8.0% were randomized either to the Continuous Glucose Monitoring System (CGMS) group or to the control group. The CGMS group used 6 3-day sensors within a 30-day period. Both groups self-monitored their blood glucose levels a minimum of 4 times daily. HbA1c levels were measured at the start, at 1-month, and after 3 months of study.\n The 5 children using the CGMS had 17 asymptomatic episodes (85%) of glucose levels below 60 mg/dL (3.25 mmol/L) and 3 symptomatic episodes (15%) during the night in the study month. The 6 control children had 4 symptomatic nocturnal low episodes during the month. After the 30-day period of wearing the CGMS, the 5 children had a significantly lower mean HbA1c value compared with their initial value (mean +/- standard error of the mean [SEM] decrease =.36% +/-.07%). The mean decrease for the controls was.2% +/-.2%. After 3 months, 4 of the 5 children who used the CGMS continued to have lower HbA1c values in comparison to their initial values (mean +/- SEM decrease = 1.04% +/-.43%). Three of the 6 control participants also had lower HbA1c values at 3 months (mean +/- SEM decrease for the group =.62% +/-.44%). No severe hypoglycemic events occurred in either the CGMS or the control groups.\n In this pilot trial, continuous subcutaneous glucose monitoring was helpful in detecting asymptomatic nocturnal hypoglycemia as well as in lowering HbA1c values without increasing the risk for severe hypoglycemia in children with type 1 diabetes.", "This randomised study was designed to investigate the impact of continuous glucose monitoring (CGM) for 48h on glycaemic control with a 3-month follow-up in patients with type 1 (T1D) or type 2 (T2D) diabetes.\n A total of 48 patients with poor glycaemic control (HbA(1c): 8-10.5%) underwent CGM for 48h using the GlucoDay((R)) system (A. Menarini Diagnostics), after which they were randomly assigned to treatment adjustments based on either their CGM profile (CGM group) or their usual self-monitoring of blood glucose (SMBG group). HbA(1c) measurement and 48-h CGM were repeated 3 months later.\n Altogether, 34 patients with either T1D (n=9) or T2D (n=25) completed the study; seven patients chose to leave the study, and seven patients in the CGM group were excluded because their baseline CGM graphs were not interpretable. HbA(1c) levels decreased significantly in the CGM group (n=14, -0.63+/-0.27%; P=0.023), but not in the controls (n=20, -0.28+/-0.21%; P=0.30). In T2D patients, the improvement associated with CGM vs SMBG was due to HbA(1c) decreases (mean: -0.63+/-0.34%; P=0.05 vs -0.31+/-0.29%; P=0.18, respectively). However, HbA(1c) did not change significantly with CGM in T1D patients. Comparisons of CGM data at baseline and after 3 months showed no significant changes in glucose control, glucose variability or hypoglycaemia. No major adverse events related to the GlucoDay system were reported.\n This is the first randomised study showing that CGM improves glycaemic control in patients with T2D.", "To evaluate the impact of continuous glucose monitoring (CGM) on quality of life (QOL) among individuals with type 1 diabetes.\n In a multicenter trial, 451 children and adults with type 1 diabetes were randomly assigned to CGM treatment or the control group. Generic and diabetes-specific QOL questionnaires were completed at baseline and 26 weeks by all participants and parents of participants <18 years old, and the CGM satisfaction scale was completed by the CGM group (participants and parents) at 26 weeks.\n After 26 weeks, QOL scores remained largely unchanged for both the treatment and the control group, although there was a slight difference favoring the adult CGM group on several subscales (P < 0.05). There was substantial satisfaction with CGM technology after 26 weeks among participants and parents.\n Baseline QOL was high, and the measures showed little change with CGM use, although a high level of CGM satisfaction was reported.", "To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS).\n Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII).\n Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus.\n The CGMS was applied for 72 hours after 1 month and at the end of each study arm.\n Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm.\n The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04).\n Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.", "This randomized crossover trial examines the effect of continuous glucose monitoring (CGM) with real-time access (RTA) to glucose data versus CGM with a retrospective analysis (RA) of glucose data regarding satisfaction with CGM and other patient-reported outcomes.\n Participants used the CGM device (GlucoDay, Menarini Diagnostics, Florence, Italy) twice. In one study phase, patients were allowed RTA to, and in the other phase RA of, current glucose values. The order of these two conditions was randomized. At baseline and after the first and second trials, subjects completed questionnaires (Continuous Glucose Monitoring Satisfaction Scale) about perceived satisfaction with CGM. They also completed the Problem Areas in Diabetes Questionnaire, a state anxiety scale (State-Trait Anxiety Inventory), and a depression scale (Center of Epidemiological Studies-Depression Scale).\n Fifty patients with type 1 diabetes (41.7 +/- 12.3 years old, diabetes duration of 14.75 +/- 11.9 years, 48% female, hemoglobin A1c 8.1 +/- 1.5%, years of education 10.3 +/- 2.1 years) participated in this study. At baseline patients perceived CGM as rather advantageous, but after RA and RTA the perceived benefits were reduced (baseline, 101.0 +/- 16.0; RA, 95.7 +/- 20.2; RTA, 93.6 +/- 22.8; P < 0.01). However, there was no significant difference between RA and RTA. Also, there was no significant effect on diabetes-related distress or state anxiety, but a positive effect on depression scores.\n There was no specific, significant, negative or positive effect of RA versus RTA on satisfaction with CGM. Exposing patients with type 1 diabetes to their current glucose values does not seem to have a specific negative impact on the appraisal of CGM or more generic patient-reported outcomes.", "Frequent blood glucose (BG) monitoring is a critical component of diabetes management, yet many barriers exist to consistent monitoring.\n In this randomized controlled trial, we sought to determine if an educational manual, the Blood Sugar Monitoring Owner's Manual (BGMOM), could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results. The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes (hemoglobin A(1C) >or=8.0%); 35% had type 1 diabetes mellitus. Participants were randomized to 1 of 3 groups: BGMOM intervention (BGM+), attention control (BG meter only [MT]), or standard care (SC). The BGM+ and MT groups received BG meters and meter education; the BGM+ group also received BGMOM booklets. The SC group received usual care. Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C) measurement.\n Monitoring frequency increased significantly in the BGM+ group (1.9 +/- 1.3 to 2.8 +/- 1.5 times daily, P<.001) but only slightly in the MT group (1.7 +/- 1.3 to 2.0 +/- 1.3 times daily). The BGM+ group experienced the greatest improvement in hemoglobin A(1C) level (BGM+: -0.13 +/- 1.28; MT: -0.04 +/- 1.31; SC: 0.04 +/- 1.10). Further, a higher percentage of those in the BGM+ group (61%) improved their glycemic control compared with the other groups (44%; P = .05). Finally, the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C) (P = .04) and reported the least amount of negative affect about out-of-range BG monitoring results (P = .03).\n As an adjunct to standard diabetes education and support, a manual such as the BGMOM can help optimize BG monitoring and glycemic control." ]

[ "16317669", "20073212", "8855091", "8841797", "15143715", "16965225", "22695903", "12585148", "9453428", "2083923", "10746839", "14687046", "2050326", "9853771", "16143129", "14643034", "6575576" ]

[ "Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid.", "[Effect of integrative Chinese and Western medicine in treating pregnant women with intrahepatic cholestasis].", "Ursodeoxycholic acid therapy in pregnant women with cholestasis.", "S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial.", "[Analysis on therapeutic effect of Western and Chinese drug in treating intrahepatic cholestasis pregnancy].", "Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy.", "Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial.", "[Observation on effect of danxiaoling in supplementary treatment of intrahepatic cholestasis in pregnancy].", "Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.", "S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.", "Oral guar gum, a gel-forming dietary fiber relieves pruritus in intrahepatic cholestasis of pregnancy.", "A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis.", "S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results.", "A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy.", "Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy.", "Cervical ripening with oral misoprostol at term.", "Use of oral oxytocics for stimulation of labor in cases of premature rupture of the membranes at term. A randomized comparative study of prostaglandin E2 tablets and demoxytocin resoriblets." ]

[ "Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP.", "To evaluate the therapeutic effect of compound salvia injection combined with ursodeoxycholic acid (UDCA) in treating pregnant women with intrahepatic cholestasis (ICP) and its influence on perinatal babies.\n One hundred and twenty-eight patients of ICP were assigned to two groups. The 72 patients in the treatment group were treated with salvia injection (20 mL in 10% glucose 500 mL for intravenous dripping once a day) and UDCA (15 mg, thrice daily by oral taken), and the 56 patients in the control group were treated with UDCA alone, all were treated for 14 days. Changes of itching symptom (estimated by scoring) and serum levels of biochemical indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and glycocholic acid (GCA), were determined before and after treatment, and conditions of the newborns were compared after delivery.\n Compared with before treatment, scores of itching were lowered from 3.6 scores to 1.4 scores in the treatment group, and from 3.4 scores to 1.6 scores in the control group, showing no significant difference between groups (P > 0.05), but the lowering was shown earlier in the former. Levels of biochemical indexes were improved significantly (P < 0.01) in both groups, but the improvements were more significant in the treatment group, the difference between groups was significant (P < 0.05). The difference between groups in the incidence of fetal distress, meconium-stained fluid and neonatal asphyxia were insignificant (P > 0.05). The birth weights of the newborns were higher in the treatment group than in the control group (3,108 +/- 236 g vs 2,681 +/- 269 g, P < 0.05).\n The combined therapy of compound salvia injection and UDCA shows better effect in treating ICP than that of UDCA alone.", "To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP) by a randomized, double-blind, placebo-controlled trial.\n Eight patients with pruritus and abnormal liver function tests received 600 mg/day of UDCA in two doses for 20 days, compared with a control group of eight patients who received placebo for 20 days.\n No adverse reactions were detected in any patient. During UDCA therapy a statistically significant improvement in pruritus, serum bile salt levels, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and total and direct bilirubin was observed. Only two patients treated with UDCA underwent cesarean sections due to reasons unrelated to the therapeutic trial. All newborns had an Apgar score >7 and normal postnatal growth.\n Although the number of patients in this study was very small, we suggest that UDCA treatment has a role in improving clinical and biochemical results in ICP.", "To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP).\n Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases.\n After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups.\n These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials.", "To evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy (ICP) and improving prognosis of perinatal newborn babies.\n Sixty in-patients of ICP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treatment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery.\n After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P < 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P > 0.05).\n Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.", "To compare the efficacy of the ursodeoxycholic acid (UDCA) and S-adenosyl-L-methionine (SAMe) monotherapy with their combined effect on intrahepatic cholestasis of pregnancy (ICP).\n We studied singleton pregnancies at <36 weeks with a moderate or severe form of ICP between January 1999 and March 2004. Patients were randomized to either oral UDCA 3x250 mg daily or 500 mg SAMe twice daily in slow running infusion for twelve days followed by oral administration of 500 mg twice daily until delivery. Intensive hematological, biochemical and fetal monitoring were carried out.\n Of the 78 women enrolled, 25 received SAMe monotherapy, 26 received UDCA, and 27 received combined therapy. Groups were initially comparable in terms of gestational age, duration of therapy, parity and biochemical characteristics. All therapies improved the pruritus. The combined therapy and the monotherapy with UDCA (later) led to improving of the serum concentrations of bile acids and transaminases compared with SAMe monotherapy (P<0.01). Combined therapy led to a faster decrease of serum concentrations of bile acids and transaminases compared with UDCA monotherapy (borderline significance). Gestational ages were similar in all groups. No adverse effects were noted on the fetuses or neonates with either therapy.\n UDCA is an effective drug in the treatment of ICP, and combined with SAMe, has probably a synergistic effect on biochemical parameters. This mode of treatment seems more effective but the effect of the successful treatment on the fetus is unclear. Therefore, the ante- and intrapartum monitoring of the fetus should be part of the management of severe forms of ICP. The project is supported by IGA MZ CR (No. NH/7376-3).", "To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions.\n First phase of a semifactorial randomised controlled trial.\n Nine consultant led maternity units, United Kingdom.\n 125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks' gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management.\n Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks' gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks' gestation).\n The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates.\n Ursodeoxycholic acid reduced itching by -16 mm (95% confidence interval -27 mm to -6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval -3 to 34); this would represent a number needed to treat of 6, but it failed to reach significance. Early term delivery did not increase caesarean sections (7/30 (23%) in the early term delivery group versus 11/32 (33%) in the expectant management group (relative risk 0.70, 95% confidence interval 0.31 to 1.57). No serious harms were noted in either trial. 22% (73/325) of eligible women participated in the drug trial and 19% (39/209) in the timing of delivery trial; both groups had a similar spectrum of disease severity to non-participants.\n Ursodeoxycholic acid significantly reduces pruritus, but the size of the benefit may be too small for most doctors to recommend it, or for most women to want to take it. Women are, however, likely to differ in whether they consider the benefit to be worthwhile. Planned early term delivery seems not to increase incidence of caesarean section, although a small increase cannot be excluded. A trial to test whether ursodeoxycholic acid reduces adverse perinatal outcomes would have to be large, but is feasible. A trial to test the effect of early term delivery on adverse fetal outcomes would have to be significantly larger and may not be feasible.\n Current Controlled Trials ISRCTN37730443.", "To evaluate the curative effect of Danxiaoling Pill (DXLP), a Chinese herbal preparation, in treating intrahepatic cholestasis in pregnancy (ICP).\n Fifty-eight cases of ICP were divided randomly into two groups and treated by DXLP and Composite Yiganling as control respectively with the other identical conventional treatment. The changes of clinical symptoms, related laboratory parameters after treatment and the condition of labor were observed.\n The total effective rate in both groups was 100%, but the markedly effective rate in the DXLP treated group was higher than that in control group (P < 0.01). Levels of blood cholyglycine acid (CGA), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, total cholesterol and low density lipoprotein were all decreased in both groups after treatment, but DXL showed a better efficacy in decreasing CGA, ALT and AST than that of Yiganling. Moreover, the amniotic fluid meconium contaminated rate, premature delivery occurrence in the DXLP group were lower than those in the control group, while the weight of newborn baby was higher in the former than in the latter.\n DXLP could effectively lower the serum bile acid and improve liver function in treating ICP.", "Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset.\n Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery.\n Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery.\n Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.", "Previous studies have shown that S-adenosylmethionine (SAMe) counteracts oestrogen-induced bile secretion failure. In order to confirm this anticholestatic activity, we conducted a single-blind clinical trial comparing SAMe with placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP). Thirty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (800 mg/day i.v.) or placebo until delivery for a mean period of 18 days. After SAMe, the women exhibited significantly (p less than 0.01) lower levels of total bile acids, serum conjugated bilirubin and aminotransferases with respect to pretreatment levels as well as to the corresponding values of the placebo group. In addition, SAMe significantly reduced pruritus whereas placebo was ineffective. No adverse reactions on mother or child were recorded during SAMe treatment, and the follow-up of these cases showed an incidence of premature labour (earlier than 37 weeks of gestation) in 2 out of 15 vs 5 out of 15 cases in the placebo group. In conclusion, these findings document that SAMe is more effective than placebo in ameliorating subjective and objective parameters of ICP.", "Guar gum is a gel-forming fiber, which increases fecal elimination of bile acids. It may therefore be beneficial in the treatment of intrahepatic cholestasis of pregnancy.\n Forty-eight patients with intrahepatic cholestasis of pregnancy were randomized double-blind to receive either guar gum or placebo until delivery. Serum bile acid concentration was measured. Pruritus was assessed by both the investigator and the patient.\n At baseline, the intensity of pruritus and the serum bile acid concentration were significantly related. Guar gum diminished or prevented worsening of pruritus, while in the placebo group pruritus was enhanced (p<0.05). In the placebo group serum bile acid concentration increased significantly, whereas in the guar gum group it remained unchanged (p<0.05 between the groups). Guar gum treatment-induced changes of the pruritus score and serum bile acid concentrations were significantly related (p<0.01).\n Guar gum relieved the intensity of pruritus without any side effects and prevented the rise in serum bile acid concentration in this placebo-controlled and double-blind study of patients with intrahepatic cholestasis of pregnancy.", "To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis.\n Randomised clinical trial.\n University hospital.\n All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001.\n Enrolled women were randomly assigned oral S-adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery.\n Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant.\n Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups.\n In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus.", "S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.", "A randomised placebo controlled study was performed in 32 women with intrahepatic cholestasis of pregnancy. The population was divided into four groups: for 20 days each group was treated only with ursodeoxycholic acid, or S-adenosylmethionine, or a combination of both drugs, or a placebo (vitamin). Itching, standard liver function tests and serum total bile acids were measured before, during, and after treatment. Itching improved in all the women as well as the biochemical abnormalities. No side-effects in the mother or in the infant were recorded during and after therapy. A combination of ursodeoxycholic acid and S-adenosylmethionine is more effective than placebo and than either drug alone.", "Treatment of intrahepatic cholestasis of pregnancy with ursodeoxycholic acid appears promising, but data are limited so far. The aim of this randomized study was to evaluate the efficacy and safety of ursodeoxycholic acid in comparison with cholestyramine.\n Eighty-four symptomatic patients with intrahepatic cholestasis of pregnancy were randomized to receive either ursodeoxycholic acid, 8-10 mg/kg body weight daily (n = 42), or cholestyramine, 8 g daily (n = 42), for 14 days. The primary end point was a reduction of pruritus by more than 50% after 14 days of treatment as evaluated by a pruritus score. Secondary end points were outcome of pregnancy, reduction of serum aminotransferase activities and serum bile acid levels, and drug safety. Intention-to-treat analysis was applied.\n Pruritus was more effectively reduced by ursodeoxycholic acid than cholestyramine (66.6% vs 19.0%, respectively; P < .005). Babies were delivered significantly closer to term by patients treated with ursodeoxycholic acid than those treated with cholestyramine (38.7 +/- 1.7 vs 37.4 +/- 1.5 weeks, respectively, P < .05). Serum alanine and aspartate aminotransferase activities were markedly reduced by 78.5% and 73.8%, respectively, after ursodeoxycholic acid, but by only 21.4%, each, after cholestyramine therapy (P < .01 vs ursodeoxycholic acid). Endogenous serum bile acid levels decreased by 59.5% and 19.0%, respectively (P < .02). Ursodeoxycholic acid, but not cholestyramine was free of adverse effects.\n Ursodeoxycholic acid is safe and more effective than cholestyramine in intrahepatic cholestasis of pregnancy.", "To determine the efficacy of 200 microg single dose oral misoprostol as a cervical priming agent at term.\n In this double-blind randomized trial, 156 pregnant women requiring induction of labor with gestational age of 37-42 weeks and Bishop score < or =5, were randomized to receive either 200 microg of misoprostol or a placebo, orally. Labor was induced with intravenous oxytocin infusion 12 h after oral medication if the patient did not go into labor. The primary outcome was the change in the Bishop score 12 h after oral medication. The secondary outcomes were the timings starting from the drug administration to the onset of uterine activity, interval between oral medication and delivery, oxytocin need for induction, mode of delivery, frequency of side effects, and neonatal and maternal outcome. The chi-square or Fisher exact test, Student's t-test, and Mann-Whitney U-test were used for analysis of the data.\n There were no significant differences in maternal characteristics or indications of induction. The Bishop score 12 h after oral medication significantly improved in the misoprostol group compared with the control group [55 (70%)>8 vs. 4 (5%)>8; P<0.001]. The induction rate was significantly reduced in the misoprostol group (P<0.001). The interval between oral medication and the onset of uterine activity was significantly shorter in the misoprostol group (P<0.001). The interval between oral medication and delivery was also significantly shorter in the misoprostol group (P<0.001). The cesarean delivery rate was significantly lower in the misoprostol group (P<0.001). There were no differences between the groups with respect to the incidence of tachysystole, hyperstimulation, adverse neonatal or maternal outcome.\n Oral administration of 200 microg single dose of misoprostol is an effective agent not only for cervical priming but also for induction of labor at term. Furthermore, it reduces the rate of cesarean deliveries.", "The efficacy of oral PGE2 tablets and buccal demoxytocin (resoriblets) for the induction of labor in cases of premature rupture of the membranes (PROM) after the 37th week of gestation has been evaluated in a prospective, randomized investigation of 193 women. PGE2 tablets (Prostin) were given to 109 parturients and demoxytocin resoriblets (Sandopart) to 84. The former were given in increasing doses from an initial 0.5 mg to a maximum of 1.5 mg every hour. The demoxytocin was administered at a constant dosage of 50 I.U. every 30 min. The treatment was unsuccessful in 10 of the women treated with PGE2 tablets and in 19 women receiving demoxytocin resoriblets. In addition, the treatment had to be discontinued in 5 women in the PGE2 group due to gastrointestinal side effects. This gives a total success rate of 86.3% for treatment with PGE2 against 77.4% in respect of demoxytocin. This difference is not significant. No difference was observed between the two treatment groups as regards: the stimulation-delivery interval, duration of the various stages of labor, efficacy in primiparae and multiparae, efficacy in patients with a high/low Bishop score. A significantly higher frequency of gastro-intestinal side effects was seen in those treated with PGE2 (21.7%) as compared with demoxytocin (3.6%). The frequency of surgical intervention was 17% in the PGE2 group and 10% in the demoxytocin group. In 4 cases where the stimulation was successful, cesarean section was carried out for reasons unrelated to the drug therapy. Despite the fact that demoxytocin treatment results in fewer side effects than PGE2, the efficacy of the drug is not superior. Based on experience from previous investigations carried out in this department, where intravenous oxytocin was found to be clearly better than oral PGE2 for the induction of labor in cases of PROM, intravenous oxytocin will remain the method of choice due to the shorter period of treatment, which must take priority." ]

[ "10379017" ]

[ "Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group." ]

[ "Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy.\n Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002).\n Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication." ]

[ "9311492", "11596162", "17675317", "12550014", "3296295", "19703826" ]

[ "Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen.", "Comparison of high-frequency chest wall oscillation and oscillating positive expiratory pressure in the home management of cystic fibrosis: a pilot study.", "Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis.", "[Non-invasive ventilation in kyphoscoliosis. A comparison of a volumetric ventilator and a BIPAP support pressure device].", "Evaluation of positive expiratory pressure as an adjunct to chest physiotherapy in the treatment of cystic fibrosis.", "Short-term comparative study of high frequency chest wall oscillation and European airway clearance techniques in patients with cystic fibrosis." ]

[ "Progressive deterioration of lung function in cystic fibrosis (CF) patients may lead to significant hypoxaemia and hypercapnia, especially during sleep. The effects of bi-level noninvasive positive pressure nasal mask ventilation (NIPPV) on respiration and sleep were compared to those of low-flow oxygen therapy in six CF patients (mean +/- SD age 22.3 +/- 4.7 yrs, with severe lung disease (forced expiratory volume in one second (FEV1) 29.4 +/- 3.4% predicted). Compared to the control night, NIPPV and oxygen therapy significantly improved overall night-time oxygen saturation during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. However, significant increases in transcutaneous CO2 tension occurred during oxygen therapy, while NIPPV markedly improved alveolar ventilation during all sleep states. Sleep architecture and arousals remained unchanged during NIPPV and oxygen therapy treatment nights. We conclude that noninvasive positive pressure ventilation improves sleep-related hypoxaemia and hypercapnia in severe cystic fibrosis patients without affecting sleep. The long-term compliance and benefits of noninvasive positive pressure ventilation remain unclear.", "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 clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg).\n In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity.\n Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2.\n 6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.", "Non-invasive intermittent positive pressure ventilation (NIPPV) at home is the treatment of choice for patients with chronic respiratory insufficiency secondary to severe kyphoscoliosis. Our aim was to compare clinical course, blood gases and lung function after one month of domiciliary NIPPV with two types of ventilator and to assess sleep pattern changes in patients enrolled in a prospective, randomized crossover study. Ten patients with chronic respiratory insufficiency due to kyphoscoliosis were enrolled and randomly assigned to the first device. After one month of use, the patients underwent clinical and functional examinations and polysomnographic studies while using the ventilator. The same protocol was applied with the second device after a ten-day washout period. Baseline polysomnographs showed fragmented sleep with low percentages of deep non-REM sleep and of REM sleep, as well as respiratory patterns characterized by very high frequencies coinciding with significant desaturations. In all cases symptoms and arterial blood gas improvements were significant, with no differences between the two treatment periods. The percentages of time spent with SaO2 below 90% of reference in sleep studies were significantly lower than baseline with both ventilators. All but one patient had better tolerance of the bilevel positive airway pressure (BIPAP) support mode than of the volumetric ventilator. Our study shows that NIPPV is equally effective for patients with kyphoscoliosis whether administered with a volumetric ventilator or a BIPAP device. Subjective response and tolerance seem to be slightly better with BIPAP.", "It has been suggested that positive expiratory pressure may assist the clearance of bronchial secretions in the treatment of cystic fibrosis. It has been compared with currently used postural drainage techniques. Three treatment regimens were compared in 18 patients with cystic fibrosis. Treatment A consisted of breathing exercises emphasising inspiration, interspersed with the forced expiration technique in gravity assisted positions; treatment B comprised breathing exercises with positive expiratory pressure alternating with the forced expiration technique in the same gravity assisted positions; and treatment C comprised breathing exercises with positive expiratory pressure and the forced expiration technique in the sitting position. During treatment A a significantly greater quantity of sputum was produced than during treatments B and C (p less than 0.025 and p less than 0.001 respectively). Treatment B produced more sputum than treatment C (p less than 0.005). There were no significant differences in arterial oxygen saturation, FEV1 or forced vital capacity. Most adolescent and adult patients are able to carry out their treatment independently using gravity assisted positions, breathing exercises emphasising inspiration, and the forced expiration technique. Sputum clearance was less effective when positive expiratory pressure was included in the treatment regimen.", "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." ]

[ "17854434", "9725926", "15586837", "17995993", "17372796", "11007655", "2030194", "19213683", "17074945", "19524389", "12634020" ]

[ "Cost-effectiveness of motivational interviewing for smoking cessation and relapse prevention among low-income pregnant women: a randomized controlled trial.", "Use and cost effectiveness of smoking-cessation services under four insurance plans in a health maintenance organization.", "Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.", "Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.", "Randomized controlled trial of a computer-based, tailored intervention to increase smoking cessation counseling by primary care physicians.", "Predictors of smoking cessation in an incentive-based community intervention.", "Evaluation of intrinsic and extrinsic motivation interventions with a self-help smoking cessation program.", "A randomized, controlled trial of financial incentives for smoking cessation.", "A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder.", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial.", "The impact of financial incentives and a patient registry on preventive care quality: increasing provider adherence to evidence-based smoking cessation practice guidelines." ]

[ "Low-income women have high rates of smoking during pregnancy, but little is known about the costs, benefits, and cost-effectiveness of motivational interviewing (MI), focused on the medical and psychosocial needs of this population, as an intervention for smoking cessation and relapse prevention.\n A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area into a randomized controlled trial of a motivational intervention for smoking cessation and relapse prevention versus usual care (UC). The findings of this clinical trial were used to estimate the costs, benefits, and cost-effectiveness of the intervention from a societal perspective, incorporating published quality-adjusted life-year (QALY) and life-year (LY) estimates. Outcomes included smoking cessation and relapse, maternal and infant outcomes, economic costs, LYs and QALYs saved, and incremental cost-effectiveness ratios.\n The cost-effectiveness of MI for relapse prevention compared to UC was estimated to be $851/LY saved and $628/QALY saved. Including savings in maternal medical costs in sensitivity analyses resulted in cost savings for MI for relapse prevention compared to UC. For smoking cessation, MI cost more but did not provide additional benefit compared to UC. In one-way sensitivity analyses, the incremental cost-effectiveness of MI versus UC would have been $117,100/LY saved and $86,300/QALY saved if 8% of smokers had quit. In two-way sensitivity analyses, MI was still relatively cost-effective for relapse prevention ($17,300/QALY saved) even if it cost as much as $2000/participant and was less effective. For smoking cessation, however, a higher level of effectiveness (9/110) and higher cost ($400/participant) resulted in higher incremental cost-effectiveness ratios ($112,000/QALY).\n Among low-income pregnant women, MI helps prevent relapse at relatively low cost, and may be cost-saving when net medical cost savings are considered. For smoking cessation, MI cost more but provided no additional benefit compared to UC, but might offer benefits at costs comparable to other clinical preventive interventions if 8-10% of smokers are induced to quit.", "Lack of information about the effect of insurance coverage on the demand for and use of smoking-cessation services has prevented widescale adoption of coverage for such services.\n In a longitudinal, natural experiment, we compared the use and cost effectiveness of three forms of coverage with those of a standard form of coverage for smoking-cessation services that included a behavioral program and nicotine-replacement therapy. The study involved seven employers and a total of 90,005 adult enrollees. The standard plan offered 50 percent coverage of the behavioral program and full coverage of nicotine-replacement therapy. The other plans offered 50 percent coverage of both the behavioral program and nicotine-replacement therapy (reduced coverage), full coverage of the behavioral program and 50 percent coverage of nicotine-replacement therapy (flipped coverage), or full coverage of both the behavioral program and nicotine-replacement therapy.\n Estimated annual rates of use of smoking-cessation services ranged from 2.4 percent (among smokers with reduced coverage) to 10 percent (among those with full coverage). Smoking-cessation rates ranged from 28 percent (among users with full coverage) to 38 percent (among those with standard coverage). The estimated percentage of all smokers who would quit smoking per year as a result of using the services ranged from 0.7 percent (with reduced coverage) to 2.8 percent (with full coverage). The average cost to the health plan per user who quit smoking ranged from $797 (with standard coverage) to $1,171 (with full coverage). The annual cost per smoker ranged from $6 (with reduced coverage) to $33 (with full coverage). The annual cost per enrollee ranged from $0.89 (with reduced coverage) to $4.92 (with full coverage).\n Use of smoking-cessation services varies according to the extent of coverage, with the highest rates of use among smokers with full coverage. Although the rate of smoking cessation among the benefit users with full coverage was lower than the rates among users with plans requiring copayments, the effect on the overall prevalence of smoking was greater with full coverage than with the cost-sharing plans.", "The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.", "To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.", "The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians.\n Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients' smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering.\n Intervention physicians exceeded controls on \"Assess\" (OR 5.06; 95% CI 3.22, 7.95), \"Advise\" (OR 2.79; 95% CI 1.70, 4.59), \"Assist-set goals\" (OR 4.31; 95% CI 2.59, 7.16), \"Assist-provide written materials\" (OR 5.14; 95% CI 2.60, 10.14), \"Assist-provide referral\" (OR 6.48; 95% CI 3.11, 13.49), \"Assist-discuss medication\" (OR 4.72;95% CI 2.90, 7.68), and \"Arrange\" (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts.\n The use of a brief computer-tailored report improved physicians' implementation of the 5As and had a modest effect on patients' smoking behaviors 6 months postintervention.", "The Quit and Win Challenge, an incentive-based intervention, was implemented in two counties in Eastern Ontario to encourage adult smokers to quit smoking. Participants (n = 231) were compared with adult smokers selected at random (n = 385) from a larger, four-county area. Baseline characteristics were assessed by telephone interview, including socio-demographic and smoking-related factors. Follow-up interviews were also conducted by telephone. Initial and follow-up response rates were high (over 84%) in both groups. Compared with the random survey group, Quit and Win participants tended to be younger, more educated, employed and heavier smokers, with fewer friends or co-workers who smoked. After one year, 19.5% of them reported that they were smoke-free, whereas less than 1% of the random group had achieved cessation. This translates into an impact rate of 0.17%, affecting 1 in 588 adult smokers. With the exception of the smokers' baseline \"stage of change,\" none of the socio-demographic or smoking factors was predictive of cessation. We conclude that this intervention achieved only limited success and attracted certain sectors of the community disproportionately, i.e. smokers who were highly motivated to quit. We argue that increased access to proven cessation therapies would improve the impact of such interventions.", "Personalized feedback and a financial incentive, developed from an intrinsic/extrinsic motivation framework, were evaluated as adjuncts to self-help materials for smoking cessation. Ss (N = 1,217) were randomized to 4 treatment groups and were followed up at 3 and 12 months. Consistent with hypotheses derived from the motivation framework, the financial incentive increased the use of self-help materials, did not increase cessation rates among program users, and was associated with higher relapse rates among those who did manage to quit. The personalized feedback increased both smoking cessation and use of the materials 3 months after distribution of the materials. Continuous abstinence (abstinence at 3 and 12 months) in the group that received the personalized feedback alone was twice the rate of the other groups.", "Smoking is the leading preventable cause of premature death in the United States. Previous studies of financial incentives for smoking cessation in work settings have not shown that such incentives have significant effects on cessation rates, but these studies have had limited power, and the incentives used may have been insufficient.\n We randomly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs (442 employees) or to receive information about programs plus financial incentives (436 employees). The financial incentives were $100 for completion of a smoking-cessation program, $250 for cessation of smoking within 6 months after study enrollment, as confirmed by a biochemical test, and $400 for abstinence for an additional 6 months after the initial cessation, as confirmed by a biochemical test. Individual participants were stratified according to work site, heavy or nonheavy smoking, and income. The primary end point was smoking cessation 9 or 12 months after enrollment, depending on whether initial cessation was reported at 3 or 6 months. Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs.\n The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment (14.7% vs. 5.0%, P<0.001) and 15 or 18 months after enrollment (9.4% vs. 3.6%, P<0.001). Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program (15.4% vs. 5.4%, P<0.001), completion of a smoking-cessation program (10.8% vs. 2.5%, P<0.001), and smoking cessation within the first 6 months after enrollment (20.9% vs. 11.8%, P<0.001).\n In this study of employees of one large company, financial incentives for smoking cessation significantly increased the rates of smoking cessation. (ClinicalTrials.gov number, NCT00128375.)\n 2009 Massachusetts Medical Society", "Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs, few studies have investigated the efficacy of smoking cessation interventions among this group. The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone.\n The authors recruited 298 regular smokers with a psychotic disorder residing in the community and randomly assigned them to a routine care comparison condition (N=151) or an eight-session, individually administered smoking cessation intervention (N=147), which consisted of nicotine replacement therapy, motivational interviewing, and cognitive behavior therapy. Outcome variables included continuous and point-prevalence abstinence rates, smoking reduction status, and changes in symptoms and functioning.\n While there were no overall differences between the treatment group and comparison group in abstinence rates, a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions (point-prevalence rates: 3 months, 30.0% versus 6.0%; 6 months, 18.6% versus 4.0%; and 12 months, 18.6% versus 6.6%). Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months (21.4% versus 4.0%). There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects. There was no evidence of any associated deterioration in symptoms or functioning.\n These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder. Further development of more efficacious interventions is required for those who do not respond to existing interventions.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260.", "This study tested the effects of two organizational support processes, the provision of financial incentives for superior clinical performance and the availability of a patient (smoker) registry and proactive telephone support system for smoking cessation, on provider adherence to accepted practice guidelines and associated patient outcomes.\n Forty clinics of a large multispecialty medical group practice providing primary care services were randomly allocated to study conditions. Fifteen clinics each were assigned to the experimental conditions \"control\" (distribution of printed versions of smoking cessation guidelines) and \"incentive\" (financial incentive pay-out for reaching preset clinical performance targets). Ten clinics were randomized to receive financial incentives combined with access to a centralized patient registry and intervention system (\"registry\"). Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients' smoking cessation behaviors.\n Patients' tobacco use status was statistically significant (P < 0.01) more frequently identified in clinics with the opportunity for incentives and access to a registry than in clinics in the control condition. Patients visiting registry clinics accessed counseling programs statistically significantly more often (P < 0.001) than patients receiving care in the control condition. Other endpoints did not statistically significantly differ between the experimental conditions.\n The impact of financial incentives and a patient registry/intervention system in improving smoking cessation clinical practices and patient behaviors was mixed. Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment." ]

[ "8673548", "18005909" ]

[ "Pilot randomized controlled trial of Chinese herbal treatment for HIV-associated symptoms.", "Efficacy of a pelargonium sidoides preparation in patients with the common cold: a randomized, double blind, placebo-controlled clinical trial." ]

[ "We wished to determine the short-term safety and efficacy of a Chinese medicinal herb preparation in treating symptoms of human immunodeficiency virus (HIV) infection in a 12-week randomized, double-blind, placebo-controlled clinical trial in a University-affiliated acquired immunodeficiency syndrome (AIDS) clinic at a public general hospital. Thirty adults with symptomatic HIV infection, no previous AIDS-defining diagnosis, and CD4+ counts of 0.200-0.499 x 10(9)/L (200-499/mm3) received 28 tablets each day of either a standardized oral preparation of 31 Chinese herbs or a cellulose placebo. Primary outcome measures were changes in life satisfaction, perceived health, and number and severity of symptoms. Other outcomes included adherence, and changes in weight, CD4+ count, depression, anxiety, physical and social function, and mental health. Two placebo- and no herb-treated subjects had mild adverse events (AE). Subjects on both arms reported taking 94% of prescribed tablets. No differences between treatment groups reached the p < 0.05 level. Life satisfaction improved in herb-treated [+0.86, 95% confidence interval (CI): +0.29, +1.43] but not in placebo-treated subjects (+0.20, 95% CI -0.35, + 0.75). Number of symptoms was reduced in subjects receiving herbs (-2.2, 95% CI -4.1, -0.3) but not in those receiving placebo (-0.3, 95% CI -3.2, +2.7). There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic. Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped (p < 0.005), but not with changes in life satisfaction or symptoms. There were improvements in life satisfaction and symptoms among subjects receiving the herbal therapy. Whether Chinese herbs are effective in the management of symptomatic HIV infection can be adequately addressed only by larger trials of longer duration.", "The common cold is a viral infection with symptoms such as sneezing, sore throat, and running nose. It is one of the most prevalent illnesses in the world, and although commonly caused by rhinoviruses, antibiotics are often prescribed unnecessarily. Therefore, it is of utmost importance to evaluate alternative treatments such as herbal medications, whose efficacy and safety is proven by pharmacological and clinical studies.\n The aim of the present study was to evaluate the efficacy of a liquid herbal drug preparation from the roots of Pelargonium sidoides compared with placebo in adult patients with the common cold.\n The study was designed as a multicenter, prospective, randomized, double blind, parallel group, placebo-controlled phase III clinical trial with an adaptive group-sequential design.\n The study took place in eight outpatient departments affiliated with hospitals.\n One hundred three male and female adult patients with at least two major and one minor or with one major and three minor cold symptoms (maximum symptom score of 40 points), present for 24 to 48 hours, and who gave provision of informed consent were randomized to receive either 30 drops (1.5 mL) of the liquid herbal drug preparation EPs or placebo three times a day.\n Patients received randomized treatment for a maximum period of 10 days.\n The primary outcome criterion was the sum of symptom intensity differences (SSID) of the cold intensity score (CIS) from day one to day five. The CIS consists of the following 10 cold symptoms: nasal drainage, sore throat, nasal congestion, sneezing, scratchy throat, hoarseness, cough, headache, muscle aches, and fever.\n From baseline to day five, the mean SSID improved by 14.6 +/- 5.3 points in the EPs group compared with 7.6 +/- 7.5 points in the placebo group. This difference was statistically significant (P < .0001). The mean CIS decreased by 10.4 +/- 3.0 points and 5.6 +/- 4.3 points in EPs and placebo-treated patients, respectively. After 10 days, 78.8% versus 31.4% in the EPs versus placebo group were clinically cured (CIS equals zero points or complete resolution of all but a maximum of one cold symptom; P < .0001). The mean duration of inability to work was significantly lower in the EPs treatment group (6.9 +/- 1.8 days) than in the placebo group (8.2 +/- 2.1 days; P = .0003). Treatment outcome (rates of complete recovery or major improvement from disease [integrative medicine outcomes scale]) was assessed better in the EPs treatment group than in the placebo group by both the investigator and the patient on day five (P < .0001). Adverse events occurred in three of 103 patients (2.9%), with two of 52 (3.8%) and one of 51 (2.0%) patients in the EPs and placebo group, respectively. All adverse events were assessed as nonserious. At the end of treatment, all patients (100%) in the active treatment group judged the subjective tolerability of EPs as good or very good.\n EPs represents an effective treatment of the common cold. It significantly reduces the severity of symptoms and shortens the duration of the common cold compared with placebo. The herbal drug is well tolerated." ]

[ "12798791", "19808135", "12499477", "17285226", "14628981" ]

[ "Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy.", "Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial.", "Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy.", "Does modafinil enhance activity of patients with myotonic dystrophy?: a double-blind placebo-controlled crossover study.", "Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study." ]

[ "Patients with myotonic dystrophy frequently suffer from excess daytime sleepiness, which can be a significant cause of disability. Previous studies have indicated that this excess daytime sleepiness is only occasionally due to obstructive sleep apnoea and may be principally of central nervous system origin. Modafinil has been successfully used to treat narcolepsy, a central disorder causing excess daytime sleepiness. We have investigated the use of this drug in myotonic dystrophy patients with excess daytime sleepiness. Patients were recruited from a clinic population on the basis of screening with the Epworth Sleepiness Scale. Patients scoring 10 and above were invited to participate in a randomized double-blind crossover trial of modafinil versus placebo, with four weeks in each arm of the study separated by a 2-week washout period. Patients were assessed by polysomnography at baseline. The primary outcome measures were change in both the Epworth Sleepiness Scale and a modified Maintenance of Wakefulness Test, which were measured at the start of each arm of the trial and in week 3 of each intervention period. In agreement with previous smaller studies, sleepiness is not correlated with CTG expansion size. Treatment with modafinil showed a non-significant reduction in median Epworth Sleepiness Scale. However, the median Maintenance of Wakefulness Test score was prolonged by treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac effects of the drug in this group of patients (resting 12 lead and 24 h ECG monitoring). Selected patients with myotonic dystrophy and excess daytime sleepiness may benefit from modafinil. In this patient group the Epworth Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the potential for cardiac disease in these patients, the drug was well tolerated with no adverse effects.", "Myotonic muscular dystrophy type 1 (MMD1) is the most common form of adult MD, with a mean prevalence of 1 in 8000. Excessive daytime sleepiness (ie, hypersomnia) is a common complication of MMD1.\n The aim of this study was to evaluate the efficacy and tolerability of modafinil for the treatment of hypersomnia in adults with MMD1.\n This multicenter, prospective, randomized, double-blind, placebo-controlled study consisted of a prerandomization period (90 to 2 days before randomization) and a 4-week randomization period in which patients were assigned to receive either active treatment (modafinil 300 mg/d) or placebo. The study was conducted at 3 clinics in France between February 2000 and June 2002. Adult patients aged > or =18 years, with genetically proven MMD1, an Epworth Sleepiness Scale (ESS) score >10, and a mean latency to sleep onset < or =8 minutes measured by the Multiple Sleep Latency Test (MSLT) were eligible. The primary efficacy end point was the Maintenance of Wakefulness Test (MWT) score at 4 weeks. Secondary end points included the mean MSLT score and scores from the ESS, physician's assessment of the therapeutic effect and the patient's global self-assessment via visual analog scale, the 17-item Hamilton Depression Rating Scale, and the Short Form Health Survey (SF-36) quality-of-life assessment.\n A total of 28 patients (15 men, 13 women; mean [SD] age, 40 [12.7] years [range, 18-69 years]; 100% white; modafinil group, 13; placebo group, 15) completed the study without protocol violations. Of the 28 patients with MMD1 included in the analysis, 21 had adult-onset MMD1. At 4 weeks, the mean MWT score was 16.4 (3.3) minutes in the modafinil group and 15.8 (3.8) minutes in the placebo group (P = NS). At the end of the randomization period, there were no significant between-group differences in any secondary outcome. A total of 8 patients (4 in each group) reported > or =1 adverse event, including digestive, neurologic, and skin symptoms. Weight loss was reported in 1 patient (2 kg).\n In this small study conducted in an adult population with MMD1 and a high prevalence of hyper-somnia, modafinil had no significant effects on daytime somnolence measured using objective MWTs.", "To evaluate the potential of modafinil in reducing excessive daytime somnolence (EDS) and enhancing indexes of quality of life and mood in patients with myotonic dystrophy (DM).\n Forty patients with DM were randomized to receive modafinil and placebo for 14 days each, using a double-blind, cross-over design. Before and after each trial, subjects completed handgrip strength testing, spirometry, and quality-of-life measures (RAND). On days 7 and 14, each subject completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the Profile of Mood States (POMS).\n ESS scores were lower while taking modafinil (mean 248 mm; 95% confidence limit 220 to 276 mm) as compared with placebo (309 mm; 281 to 336 mm) (p < 0.001). Mean SSS scores were also lower during the modafinil trial (3.05; 2.77 to 3.33) than during the placebo trial (3.45; 3.18 to 3.71) (p < 0.05). The POMS indicated that modafinil decreased fatigue-inertia (p < 0.001) and increased vigor-activity and tension-anxiety (p < 0.001) indexes. The total mood disturbance score was also decreased during the modafinil trial as compared with placebo (p < 0.05). The RAND quality-of-life measures of energy (p < 0.001) and health change (p < 0.05) were both significantly enhanced during the modafinil treatment phase. No changes in maximal grip strength or forced expired volume in 1 second were detected over the course of the study. Headache was the most frequently reported adverse event. Four patients withdrew from the study, three because of side effects (two during modafinil ingestion and one during placebo ingestion).\n Modafinil reduces somnolence and improves mood in patients with DM.", "We performed a double-blind placebo-controlled crossover study in 13 patients with myotonic dystrophy to address the question whether modafinil, known to improve hypersomnolence in myotonic dystrophy, may improve levels of activity as well. We used the Epworth Sleepiness Scale as a measure of hypersomnolence and a structured interview of the patient and the partner or housemate as a measure of activity. We additionally used a restricted form of the RAND-36 to relate a possible improvement of activity to perceived general health. We confirmed earlier positive findings of modafinil regarding reduced somnolence (p=0.015), but no significant effects were seen regarding activity levels (p=0.2 for patients' self-reports and 0.5 for partners' reports).", "Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants.\n Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study.\n One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants.\n Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy." ]

[ "1728157" ]

[ "A double-blind comparison of valproate and lithium in the treatment of acute mania." ]

[ "This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.\n Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).\n At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.\n Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states." ]

[ "14681639", "8245265", "2403699", "1920650", "15580451", "14974959" ]

[ "Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers.", "Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers.", "Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula.", "A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report.", "[Venous leg ulcers: no improvement of wound healing with 685-nm low level laser therapy. Randomised, placebo-controlled, double-blind study].", "Bacterial load in relation to vacuum-assisted closure wound therapy: a prospective randomized trial." ]

[ "Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.\n This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.\n Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.\n Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.", "Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers.\n Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers.\n Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment.\n No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different.\n CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.", "Chronic, nonhealing, cutaneous ulcers are a serious clinical problem. The results of previous studies using platelet-derived wound healing formula (PDWHF), derived from autologous platelets, provided evidence that PDWHF actively stimulates repair of the wound. To test whether or not PDWHF accelerates repair, a prospectively randomized, blinded trial was conducted using a placebo control. A total of 32 patients with chronic, nonhealing, cutaneous wounds of the lower extremity were randomized and treated for eight weeks with PDWHF or placebo. Epithelialization of the wound was the end point of study. In the group who received treatment, 81 per cent of patients had epithelialization in eight weeks compared with 15 per cent in the control group (p less than 0.0001). After crossover to treatment with PDWHF, all of the patients in the control group had epithelialization in an average of 7.1 weeks. Regression analysis of the rates of epithelialization also showed significant differences during the initial eight week trial and showed no difference after crossover of the control group to therapy with PDWHF. Results from this study demonstrate a highly statistically significant effect of topically applied platelet-derived growth factors on the repair of chronic, nonhealing, cutaneous ulcers.", "Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS)", "Venous leg ulcers (ulcera crurum venosa) are frequently seen in elderly patients. It has been suggested that low level laser irradiation has a biostimulative and wound healing effect; however, this has not yet been clinically verified by controlled studies.\n The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients randomised into two treatment groups (685-nm low level laser and placebo laser) or a control group which served to quantify the effect of laser application. All patients received standardized wound care.\n The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo \"light source\". The size of the ulcers was planimetrically measured at baseline (day 1), at the end of therapy (day 28) and 2 months later (day 90). The difference in wound size was evaluated.\n There were no statistically significant differences in reduction of wound size between the three groups, thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa.", "Vacuum-assisted closure has become a new technique in the challenging management of contaminated, acute, and chronic wounds. Although promising clinical results have been described, scientific proof to substantiate the mechanism of action of this therapy is scarce. In the present study, we examined whether the positive effect on wound healing found in vacuum-assisted closure-treated wounds could be explained by an effect on the bacterial load. Fifty-four patients who needed open wound management before surgical closure were included in this study. Wounds were randomized to either vacuum-assisted closure therapy (n= 29) or treatment by conventional moist gauze therapy (n= 25). Healing was characterized by development of a clean granulating wound bed (\"ready for surgical therapy\") and reduction of wound surface area. To quantify bacterial load, biopsies were collected. No significant difference was found in time needed to reach \"ready for surgical therapy\" comparing both therapies. Wound surface area reduction was significantly larger in vacuum-assisted closure-treated wounds: 3.8 +/- 0.5 percent/day (mean +/- SEM) compared to conventional-treated wounds (1.7 +/- 0.6 percent/day; p < 0.05). The total quantitative bacterial load was generally stable in both therapies. However, nonfermentative gram negative bacilli showed a significant decrease in vacuum-assisted closure-treated wounds (p < 0.05), whereas Staphylococcus aureus showed a significant increase in vacuum-assisted closure-treated wounds (p < 0.05). In conclusion, this study shows a positive effect of vacuum-assisted closure therapy on wound healing, expressed as a significant reduction of wound surface area. However, this could not be explained by a significant quantitative reduction of the bacterial load." ]