A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants

BACKGROUND: Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. METHODS: We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered. RESULTS: The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups. CONCLUSIONS: Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages.     

Octreotide in the prevention of hyperamylasemia following ERCP (a controlled multicenter study)

The aim of the multicentric trial was to study the effect of octreotide (Sandostatin) on the rise of pancreatic amylase in the serum after ERCP based on a large number of patients. The study was carried out in a prospective random manner in 2102 patients in 11 endoscopic centers. Patients in the treated group received 0.1 mg octreotide acetate, and those of the nontreated (control) group received isotonic sodium-chloride subcutaneously before the ERCP and 45 minutes after. Serum amylase and blood sugar were checked before the endoscopic procedure, 6 and 24 hours later. Out of the total number of patients involved, data of 1199 patients (599 in the treated group, and 600 in the control group) were evaluated. Octreotide diminished the percentual increase of serum amylase levels following ERCP. However, the frequency of hyperamylasaemia was decreased only after in patients with chronic obstructive pancreatitis or in such patients after endoscopic sphincterotomy. The peak serum level of blood sugar was higher in the treated group compared to the controls. There was no difference in the clinical symptoms following ERCP between the two groups. Conclusion: the prophylactic use of long-acting somatostatin may diminish the frequency of hyperamylasemia after ERCP in patients with chronic obstructive pancreatitis or in those patients who subsequently underwent EST.     

The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients

BACKGROUND: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study. METHODS: Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15). RESULTS: The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment. CONCLUSIONS: The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.     

Implementation of the Ottawa ankle rules in France. A multicenter randomized controlled trial

OBJECTIVES: To assess the impact of the implementation of the Ottawa ankle rules on radiography requests in French hospitals during a 5-month intervention period and the impact of using posters alone to sustain the effect of the rules during a 5-month postintervention period. DESIGN: Multicenter randomized controlled trial preceded and followed by observational studies of radiological practices. SETTING: The emergency departments of 5 Paris university teaching hospitals of the Assistance Publique-H?pitaux de Paris. PATIENTS: A total of 2218, 1911, and 851 patients-all aged 18 years and older-who were seen for acute ankle or midfoot injuries in emergency departments during preintervention, intervention, and postintervention periods, respectively. INTERVENTION: Implementation of the Ottawa ankle rules by emergency department physicians in the intervention hospitals (using meetings, posters, pocket cards, and data forms). During the postintervention period, posters alone were used to sustain the intervention effect. MAIN OUTCOME MEASURE: Percentage of patients for whom radiography was requested. RESULTS: During the preintervention period, 98% and 98.5% of patients were referred for radiography in the intervention and control groups, respectively. During the intervention period, the mean proportions of patients referred for radiography by physicians was 78.9% in the intervention group and 99% in the control group (P=.03). Between preintervention and intervention periods, a relative reduction of 22.4% (95% confidence interval [CI], 19.8%-24.9%) in radiography requests was observed in the intervention group, while requests increased by 0.5% (95% CI, 0%-1.4%) in the control group. During the postintervention period, the proportion of radiography requests in the intervention hospitals was lower than the proportion observed in the preintervention period (83.1% vs 98%). CONCLUSIONS: Implementation of the Ottawa ankle rules significantly reduced radiography requests in French hospitals. Using a minimal postintervention implementation strategy, the effect of this intervention decreased but persisted after it was discontinued.     

Results of a multicenter trial of the CapSure (Re/Stor) Continence shield on women with stress urinary incontinence

OBJECTIVES: To prospectively study the impact of the CapSure (Re/Stor) Continence shield for the treatment of stress urinary incontinence. METHODS: One hundred women with pure stress urinary incontinence were enrolled in a 6-month study. Objective measures of urine loss included pad weight test (PdWt) and provocative stress test (PST). Subjective measures included incontinence diaries documenting the number of incontinence episodes per day (IEPD), quality of life questionnaires, and satisfaction surveys. Objective and subjective measures were performed prior to enrollment, during use of the CapSure shield, and after discontinuation of the device. RESULTS: During the 12-week device utilization period, PdWt measurements demonstrated a 96% reduction in urine loss by week 1 and 97% by week 12. Eighty-two percent of subjects were completely dry by week 12. PST demonstrated 100% reduction in urine loss at each visit, with 91% of subjects completely dry by week 12. IEPD also demonstrated a 91% reduction in incontinence episodes by week 12. Quality of life scores and patient satisfaction surveys demonstrated significant improvement. During the 6-week post device utilization period (PUP), subjects continued to demonstrate a reduction in urine loss compared to pre-enrollment data, despite discontinuation of use. PdWt measurements demonstrated a 73% and 79% reduction in urine loss at weeks 14 and 18, respectively. Measurements of PST and IEPD demonstrated significant reductions in urine loss at weeks 14 and 18. A 1.5% prevalence of positive urine cultures was noted during device use. Bothersome vaginal or urethral irritation occurred in 12% of patients. Adverse events were few and required no therapeutic intervention. CONCLUSIONS: The CapSure shield is a safe and efficacious method of managing stress urinary incontinence in women.     

Detection of human papillomavirus infection by the nucleic acid hybridization method (a multicenter study)

The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors.     

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina. A multicenter trial

BACKGROUND: Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. METHODS AND RESULTS: Patients were randomized to one of two doses of heparin (n = 50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n = 113) (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg.kg-1.h-1 r-hirudin regimens were significantly lower than with 0.05 mg.kg-1.h-1 r-hirudin; levels with 0.1- to 0.2-mg.kg-1.h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg.kg-1.h-1 hirudin. At 24 hours, they were higher with the 0.05-mg.kg-1.h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. CONCLUSIONS: Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.     

A trial of the long-term use of Sedacorone (amiodarone) under polyclinic conditions for the prevention of paroxysms of atrial fibrillation

Sedacorone (amiodarone) was given to 70 outpatients with coronary heart disease for 1.5-2 years to prevent paroxysms of cardiac arrhythmia after recovery of sinus rhythm. Sedacorone was administered initially in the dose 600 mg/day for 10-12 days, then the dose lowering was adjusted to the tolerance, heart rate and ECG readings. The minimal dose of 200 mg/day was taken for 5 days a week with a 2-day interval. In adequate individual dose Sedacorone prevented paroxysms of cardiac fibrillation or made the paroxysms less frequent in 91.4% of patients. Careful selection of patients and regular control helped avoid serious cardial and extracardiac complications. Sedacorone is recommended as a first-line medicine for outpatients with frequent paroxysms of cardiac fibrillations after recovery of the sinus rhythm to prevent the paroxysms recurrences.     

Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.     

A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding

Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.     

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.     

A randomized controlled clinical trial of increased dietary iron in breast-fed infants

Six-month-old breast-fed infants were randomly allocated to a high iron (8.2 +/- 2.9 mg/day, n = 36) weaning diet or a control group (5.2 +/- 3.4 mg/day, n = 26). We could detect no effect of increased iron intake from weaning foods on iron status of these iron-sufficient infants at 12 months.     

Renal excretion of xanthurenic acid as an index of vitamin B6 allowance in infants

Renal excretion of xanthurenic acid without any tryptophan load, passage of 4-pyridoxic acid with diurnal urine and its excretion with urine collected during 1 hour in the morning on an empty stomach were investigated in 86 practically healthy infants and in 77 others with acute respiratory viral infections aged from two weeks to one year. Investigations of the tryptophan tolerance in infants yielded negative results, viz. on administering to them of D,L-tryptophan in a load dose the infants started vomiting. Practically healthy infants did not excrete xanthurenic acid, while the renal excretion of 4-pyridoxic acid remained within normal limits. In patients at the height of the disease the passage of 4-pyridoxic acid steeply increased. In 9 of them xanthurenic acid appeared in the diurnal urine. In the quiscent stage of the affection in two infants xanthurenuria continued against the general background of diminished excretion of 4-pyridoxic acid. There is no reason to relate the disclosed xanthurenuria in sick infants with the state of hypovitaminosis in them.     

A randomized, controlled trial of aminophylline in ventilatory weaning of premature infants

OBJECTIVES: To determine whether maximal inspiratory force predicts successful neonatal extubation, and whether aminophylline affects maximal inspiratory force or the success rate of extubation. DESIGN: Double-blind, prospective, randomized, placebo-controlled trial. SETTING: Tertiary level neonatal intensive care unit. PATIENTS: A total of 20 ventilated, preterm, newborn infants: birth weight < 2.5 kg; gestation < 35 wks. INTERVENTIONS: Intravenous aminophylline 4 mg/kg bolus followed by 2.5 mg/kg every 6 hrs x three doses, then 1.5 mg/kg every 6 hrs; or placebo. Drug administration began when infants were receiving an FIO2 of < 0.4 and were progressively weaning from assisted mechanical ventilation. A standardized weaning protocol was instituted, and patients were extubated when they were able to tolerate a mechanical ventilatory rate of < 5 cycles/min. MEASUREMENTS AND MAIN RESULTS: Occlusion pressures, including maximal inspiratory force, were measured before aminophylline and daily until endotracheal extubation. Arterial blood gases were measured every 3 hrs, and 24-hr cardiac and respiratory recordings were performed postextubation. Three of ten aminophylline-treated patients failed extubation compared with two of ten placebo infants (p = nonsignificant). Mean apnea frequency postextubation was 0.02/hr in the aminophylline group compared with 0.3/hr in the placebo group (p < .05). Aminophylline had no effect on successful extubation or on maximal inspiratory force. Maximal inspiratory force was not correlated with the success of extubation. Apnea frequency postextubation was significantly reduced by aminophylline. CONCLUSIONS: Aminophylline is an effective prophylaxis for postextubation apnea in the preterm infant but does not affect maximal inspiratory force or increase the success rate of extubation in this patient population.     

Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked immunosorbent assay (ELISA) with radioimmunoassay methods: a multicenter study

Several methods are available for the measurement of antibodies to glutamic acid decarboxylase (anti GAD). These antibodies are valuable tools for the immunodiagnosis of insulin-dependent (type 1) diabetes mellitus (IDDM) and for the assessment of risk for the future development of IDDM. We here describe a new enzyme-linked immunosorbent assay (ELISA) for the detection of anti-GAD which was tested in a multicenter study. The results of the new anti-GAD ELISA correlate well with those obtained by radioimmunoassays (RIA) and they have a higher sensitivity (69%) and specificity (98%) compared to other anti-GAD enzyme immunoassays as determined in the IDW Proficiency Test Program for the detection of GAD antibodies. The new ELISA is simple and easy to perform, with convenient handling of the reagents. Quantitative and reproducible test results are available within approximately four hours. The new anti-GAD ELISA can be used for large scale population screening to indicate a prediabetic state as well as to diagnose autoimmune diabetes in adults (LADA) and the risk for IDDM in pregnant women with gestational diabetes.     

Transcatheter occlusion of patent ductus arteriosus with a new detachable coil system (DuctOcclud): a multicenter clinical trial

A comparison of two methods: analytical and calculation on an estimation of dietary intakes of nitrate and nitrite from six different types of general hospital diets was studied. Studies were performed in the winter season of 1996-1997. It was found that the mean daily intake of nitrates was 85 mg per person in the analytical method, and 65 mg per person in the calculated method. The estimation of average dietary intakes of nitrite was adequate: 1.67 mg per person (the analytical method) and 1.18 mg per person (the calculated method). The main source of nitrates were vegetables, whereas the main source of nitrites was meat and meat-containing products. We suggest that the different methodologies, analytical and calculation methods, for measuring dietary intakes of nitrate and nitrite from diets make it possible to make direct comparisons of intakes.