Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Corticosteroids in COPD. A clinical trial and reassessment of the literature. Effects of long-term treatment with corticosteroids in COPD. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease. Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD? The effect of dexamethasone on side effects after coronary revascularization procedures. Morbidity associated with systemic corticosteroid preparation for coronary artery bypass grafting in patients with chronic obstructive pulmonary disease: a case control study. Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome. Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. Randomised trial of corticosteroids in the treatment of tuberculous pleurisy. The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour. Adverse effects of inhaled corticosteroids in funded and nonfunded studies. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. High-dose corticosteroids in patients with the adult respiratory distress syndrome. Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease. Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial--thyroid hormone replacement in neonates. Influence of methylprednisolone on levels of neuron-specific enolase in cardiac surgery: a corticosteroid derivative to decrease possible neuronal damage. Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma. Population-based case-control study of teratogenic potential of corticosteroids. Treatment of chronic obstructive pulmonary disease with corticosteroids. Comparison of daily vs alternate-day therapy. Early administration of corticosteroids in emergency room treatment of acute asthma. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. A controlled study of the effects of single doses of hydrocortisone on the resolution of acute attacks of asthma. [Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims. Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass. The effect of oral corticosteroids on bronchodilator responses in COPD. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. Corticosteroid therapy of pulmonary sarcoidosis. A prospective evaluation of alternate day and daily dosage in stage II disease. Pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation. A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study. Effect of hormone therapy on mortality rates among women with heart failure and coronary artery disease. Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients? The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group. Quality of life is improved by endoscopic surgery and fluticasone in nasal polyposis with asthma.
The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?"
                A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.
                No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.
                This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids. A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects. To determine the effectiveness of treatment with corticosteroids in patients with COPD.
                In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.
                Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.
                Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD. Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. An exaggerated inflammatory response has been proposed to be one etiological factor.
                To test whether intravenous corticosteroid administration after cardiac surgery prevents AF after cardiac surgery.
                A double-blind, randomized multicenter trial (study enrollment August 2005-June 2006) in 3 university hospitals in Finland of 241 consecutive patients without prior AF or flutter and scheduled to undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement.
                Patients were randomized to receive either 100-mg hydrocortisone or matching placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 hours during the next 3 days. In addition, all patients received oral metoprolol (50-150 mg/d) titrated to heart rate.
                Occurrence of AF during the first 84 hours after cardiac surgery.
                The incidence of postoperative AF was significantly lower in the hydrocortisone group (36/120 [30%]) than in the placebo group (58/121 [48%]; adjusted hazard ratio, 0.54; 95% confidence interval, 0.35-0.83; P = .004; number needed to treat, 5.6). Compared with placebo, patients receiving hydrocortisone did not have higher rates of superficial or deep wound infections, or other major complications.
                Intravenous hydrocortisone reduced the incidence of AF after cardiac surgery.
                clinicaltrials.gov Identifier: NCT00442494. Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.
                In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.
                Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.
                Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD. Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.
                In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.
                All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).
                Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective. Corticosteroids decrease side effects after noncardiac elective surgery. We designed this randomized, double-blinded, placebo-controlled study to test the hypothesis that standard doses of dexamethasone (4 mg x2) would reduce postoperative nausea, vomiting, and pain, decrease the incidence of atrial fibrillation (AF), and improve appetite after cardiac surgery, thereby facilitating the recovery process. A total of 300 patients undergoing coronary revascularization surgery were enrolled in this clinical study. The anesthetic management was standardized in all patients. Dexamethasone (4 mg/mL) or saline (1 mL) was administered after the induction of anesthesia and a second dose of the same study drug was given on the morning after surgery. The incidence of AF was determined by analyzing the first 72 h of continuously recorded electrocardiogram records after cardiac surgery. The patients were assessed at 24- and 48-h intervals after surgery, as well as at the time of hospital discharge, to determine the incidence and severity of postoperative side effects (e.g., nausea, vomiting, pain) and patient satisfaction scores. Dexamethasone significantly reduced the need for antiemetic rescue medication on the first postoperative day (30% versus 42%), and the incidences of nausea (15% versus 26%) and vomiting (5% versus 16%) on the second postoperative day (P < 0.05). In addition, dexamethasone significantly reduced the percentage of patients with a depressed appetite on the second postoperative day. However, the corticosteroid failed to decrease the incidence of AF (27% versus 32%) or the total dosage of opioid analgesic medication administered in the postoperative period. We conclude that dexamethasone (8 mg in divided doses) was beneficial in reducing emetic symptoms and improving appetite after cardiac surgery. However, this dose of the corticosteroid does not seem to have antiarrhythmic or analgesic-sparing properties.
                Dexamethasone (8 mg IV) was beneficial in reducing emetic symptoms and increasing appetite after cardiac surgery. However, this dose of the corticosteroid failed to decrease postoperative pain or the incidence of new-onset atrial fibrillation. Coronary artery bypass grafting (CABG) is associated with high morbidity in patients with chronic obstructive pulmonary disease (COPD).We examine the effect of preoperative systemic corticosteroids on morbidity in this setting.
                Ninety candidates for elective CABG participated in a prospective, open randomized trial, including 30 patients with COPD who received a single injection of a long-acting corticosteroid, 30 with COPD who received placebo, and 30 without COPD who served as controls. Primary end-points were postoperative pulmonary and nonpulmonary complications. Secondary end-points were length of hospital stay (LOS), ICU stay of less than 24 hours and more than 48 hours, duration of mechanical ventilation, and time to walking and sitting.
                The rate of pulmonary complications was similar in the two COPD groups and in the COPD patients and controls. The placebo group had more major nonpulmonary complications than the treatment group, but the difference was not statistically significant (26% vs. 17%, P = NS). The non-COPD control group had significantly fewer nonpulmonary complications than the COPD patients (treatment+placebo) (33% vs 70%, P = 0.014) and a similar rate of pulmonary complications. There was a statistically significant difference between the treated and placebo COPD groups in ICU stay less than 24 hours (P < or = 0.001) and more than 48 hours (P = 0.03) and hospital stay (P = 0.013). On stepwise analysis, only age and number of coronary grafts were predictors of pulmonary complications.
                The use of preoperative systemic corticosteroids in patients with COPD undergoing CABG may shorten ICU and hospital stay. To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.
                Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.
                More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.
                These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted. A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years. In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.
                The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.
                An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.
                Thirty-one adult CAP patients who required hospitalization were enrolled.
                Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.
                In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy. To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.
                We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second < or = 55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 micrograms of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids.
                Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume.
                Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study. Tuberculous pleurisy can result in pleural fibrosis, calcification and thickening. To prevent these complications, corticosteroids are frequently used in addition to antituberculous drugs; however, new therapeutic regimens can control the disease and minimise the sequelae, and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy.
                Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months. Additionally, they were randomly assigned to a double blind treatment with either prednisone (1 mg/kg/day for 15 days and then tapering off) or placebo during the first month of treatment. Different clinical, radiological, and functional parameters were evaluated to assess the effect of corticosteroids.
                Fifty seven patients received prednisone and 60 placebo. At the end of the treatment the clinical outcome, the rate of reabsorption of the pleural fluid, the pleural sequelae, as well as lung capacity were similar in both groups.
                Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy. In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour. Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids.
                We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria.
                Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33).
                The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs. Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.
                We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.
                At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.
                These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).
                Copyright 2006 Massachusetts Medical Society. The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates.
                A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use.
                Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0. 82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups.
                Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks' gestation. Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.
                10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797.
                Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05).
                Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear. Oral systemic corticosteroids are the mainstay of treatment for problematic hemangiomas; however, current information is based on anecdotal experience and retrospective studies. We aimed to determine whether systemic steroids are efficacious in proliferating hemangioma and to compare the efficacy and safety of 2 corticosteroid treatment modalities.
                Twenty patients with problematic hemangiomas of infancy were randomly assigned to either daily oral prednisolone or monthly intravenous pulses of methylprednisolone. Their clinical outcomes (improvement using a visual analog score) and adverse events were compared at 3 months from baseline and 1 year of age. Data on possible surrogate markers of angiogenesis were available for the first 3 months.
                At 3 months, orally treated patients had a median visual analog score of 70 compared with 12 in the intravenous group. This response pattern was similar at the patients' first birthday: 50.0 vs -1.5. Additional treatment beyond 3 months was needed for 65% of the patients (7 in the intravenous and 6 in the oral group). Six of 8 patients with impaired vision at enrollment had an improved function at 1 year (4 patients in the intravenous group and 3 patients in the oral group). Of the 4 surrogate markers of angiogenesis measured (plasma basic fibroblast growth factor, vascular endothelial growth factor, vascular cellular adhesion molecule 1, endoglin, and urine basic fibroblast growth factor), the only 2 that decreased over time were vascular cellular adhesion molecule 1 and endoglin. Patients in the oral group had a higher rate of adverse effects, such as hypertension (18.6% vs 13.1%), abnormal cortisol (78% vs 60%), and growth retardation.
                Systemic corticosteroids are efficacious in stopping the proliferation of hemangiomas. The oral corticosteroids offered more clinical and biological benefit than the pulse steroids with higher risk of adverse effects. Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome. It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.
                Copyright 2000 Academic Press. The THORN trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that administration of triiodothyronine (T(3)) and hydrocortisone would decrease mortality and respiratory morbidity in preterm infants of less than 30 wk gestation. Two hundred fifty-three infants were randomized to receive either 6 micro g.kg(-1).d(-1) of T(3) with 1 mg.kg(-1).d(-1) of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion for 7 d. The dose was halved on d 5. Our first primary outcome was death or ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2 wk. The overall mortality rate for both groups was 11.4%. Relative risk of death or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p = 0.2, and death or oxygen dependence at 2 wk, 1.00, p = 0.9. We examined the relationship between free T(3) (FT(3)) and free thyroxine (FT(4)) levels in the first 7 d and the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We found significant positive correlations of p = 0.05 for FT(3) and p = 0.002 for FT(4). Thus the higher the FT(3) and FT(4) levels, the better the outcome. No beneficial effects of T(3) and hydrocortisone were shown. In this study, although FT(3) levels were doubled by the treatment infusion, FT(4) levels were significantly suppressed. The lack of any beneficial effect of T(3) in our study may be explained by suppression of FT(4) in the treatment group. Cerebral injury is a well-known complication after cardiac surgery with cardiopulmonary bypass (CPB), especially in adult patients. Specific biochemical markers like neuron-specific enolase (NSE) and S-100beta protein were developed previously for early detecting neuronal damage after CPB. Corticosteroids are shown to reduce multisystemic deleterious effects of cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of this study is to demonstrate the decrease of serum neuron-specific enolase levels in patients who received corticosteroids before CPB.
                Thirty patients scheduled for elective coronary bypass surgery were included in the study. Patients were divided randomly into two groups as the control group (n = 15) who underwent a standard coronary bypass surgery without any additional medication and the study group (n = 15) who received 1 gm of methylprednisolone before CPB. Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation.
                Serum cytokine and NSE levels were significantly increased after CPB above their normal range in both groups. In the study group, IL-6 and NSE levels were significantly reduced while IL-10 levels were much higher after CPB. High NSE levels significantly correlated with IL-6 levels in the control group.
                The lower levels of NSE in patients who received methylprednisolone may suggest that corticosteroids might be useful in decreasing possible neuronal damage during heart surgery. However, we were not able to demonstrate an adverse neurological outcome. Patients with severe asthma who require long-term oral corticosteroid therapy are at risk of unwanted effects. Several immunosuppressive drugs have been assessed as corticosteroid-sparing agents in chronic asthma. We previously showed that cyclosporin A (CsA) administered for 12 wk improved lung function in corticosteroid-dependent patients. We have now investigated the corticosteroid-sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39 corticosteroid-dependent asthmatic patients were randomized to receive CsA (19 patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk. Attempts were then made by a physician ignorant of the trial therapy to reduce their prednisolone dosages at 14-d intervals, provided that a patient's asthma remained stable or improved. Three patients receiving CsA had to be withdrawn from the study before they completed 12 wk of therapy. The remaining 16 patients achieved a statistically significant reduction in median daily prednisolone dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in the patients taking placebo (p = 0.043). This reduction was most pronounced during the last 12 wk of active therapy. In addition, morning peak expiratory flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active-treatment group but not in the placebo group (p = 0.026 between groups). Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia, were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as compared with placebo, allowed a significant reduction in oral corticosteroid dosages in patients with severe asthma, and also improved lung function. The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans. We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease. In this double-blind study, 44 patients with moderate to severe COPD (mean FEV1 740 +/- 310 ml) were hospitalized and randomly allocated to receive methylprednisolone, 8 mg qid, 64 mg qod, or placebo for a ten-day period. The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups, but not in the placebo-treated group. Eight of the 29 steroid-treated patients (28 percent) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients. Those in the qod group also had notable improvement in SaO2. Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant, some patients had more than a 25 percent improvement in their FEV1 with corticosteroids, but less than a 10 percent improvement after nebulized bronchodilators. We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration. Since the response to a qod regimen is comparable to that of a qid regimen, and since the qod regimen is associated with fewer side effects, we recommend that a qod regimen be tried initially. 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.
                Randomized, double-blind, placebo-controlled trial.
                The emergency room of a large, urban hospital with primary and referral care responsibilities.
                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.
                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.
                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.
                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. Improvement in health-related quality of life is a major object of cardiac surgery. However, high stress exposure during the perioperative period of cardiac surgery can result in the formation of traumatic memories and symptoms of chronic stress or even posttraumatic stress disorder, which can have negative effects on health-related quality-of-life outcome. In this controlled study we examined whether exogenously administered stress doses of hydrocortisone during cardiac surgery reduce perioperative stress exposure and the long-term incidence of chronic stress symptoms and improve health-related quality of life after cardiac surgery.
                Thirty-six high-risk patients undergoing cardiac surgery were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Of 28 available patients at 6 months after cardiac surgery, 14 had received hydrocortisone, and 14 had received placebo. Traumatic memories, chronic stress symptoms (posttraumatic stress disorder scores), and health-related quality of life were measured by using validated questionnaires.
                Compared with patients from the placebo group, patients from the hydrocortisone group had a significantly shorter duration of intensive care unit treatment, required lower doses of the stress hormone norepinephrine during cardiac surgery, and had significantly fewer stress symptoms and a better health-related quality of life regarding physical function, chronic pain, general health, vitality, and mental health during follow-up. The groups did not differ with regard to the number or type of intensive care unit-related traumatic memories.
                The use of stress doses of hydrocortisone in high-risk cardiac surgical patients reduces perioperative stress exposure, decreases chronic stress symptoms, and improves health-related quality of life at 6 months after cardiac surgery. Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.
                To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.
                Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.
                Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo.
                In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings. Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.
                To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.
                Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.
                Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.
                Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.
                Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).
                One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.
                In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events. Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial.
                A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy.
                Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms.
                Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia. To evaluate the effects of corticosteroids on the resolution of acute attacks of asthma, 38 young, acutely ill, asthmatic subjects were given a single intravenous injection of either 0.25, 0.50 or 1.0 g of hydrocortisone hemisuccinate or a placebo (sterile saline solution) in a random, double blind manner. Each was then treated with isoproterenol, at hourly intervals, for a minimum of six hours, and the serial changes in plethysmography, spirometry, lung volumes, subjective complaints and physical findings that occurred as the patients improved were observed. No statistical differences were found in any of the physiologic or clinical variables between those patients given any dose of steroids and their matched controls. From this it has been concluded that hydrocortisone, in the doses and route of administration employed, does not produce any immediate benefits in the treatment of acute asthma. The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.
                Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.
                131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.
                Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars. This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking. The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population. Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism.
                Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery.
                After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure.
                Extravascular fluid but not extravascular lung water is increased in patients after surgery with cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg-1 dexamethasone before coronary bypass grafting decreases extravascular fluid gain and seems to improve postoperative cardiovascular performance. This effect is not caused by a better intravascular volume status. There have been suggestions that corticosteroid treatment might improve bronchodilator responses in chronic obstructive pulmonary disease (COPD). We have studied bronchodilator responses to salbutamol and to oxitropium bromide in 20 patients with stable moderate to severe COPD. Dose responses to the two bronchodilators were tested before and after 3 week courses of placebo and 30 mg prednisolone. Thirteen patients were taking inhaled corticosteroids. There were no significant changes in numbers of responses or maximum bronchodilator effects from either bronchodilator, although there was a trend towards higher maximum levels after 3 weeks of prednisolone. Spirometry measured at home each morning before and after oxitropium bromide showed no difference between prednisolone and placebo periods. This study provides no evidence for a significant effect on bronchodilator responses to beta-agonists or anticholinergic agents from 3 weeks of oral prednisolone in moderately severe COPD. To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients. Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years duration and not treated earlier with corticosteroids were randomly allocated for treatment with methylprednisolone for 7 months or for observation without therapy. Every other treated patient was given the drugs daily and every other followed an alternate-day regimen. After 7 months the chest radiographic finding, the forced vital capacity and the diffusion capacity for carbon monoxide were superior in the treated group. There was no difference between the two drug regimens. After 24 and 48 months no statistically significant differences between the untreated and the treated groups were found. Numerous clinical studies suggest that methylprednisolone may facilitate early tracheal extubation after cardiac surgery, yet no investigation has rigorously examined the use of the drug in this setting. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting (CABG) and early tracheal extubation. Sixty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group MP patients received i.v. methylprednisolone (30 mg/kg during sternotomy and 30 mg/kg during initiation of cardiopulmonary bypass) and Group NS patients received i.v. placebo at the same two times. Perioperative management was standardized. Alveolar-arterial (A-a) oxygen gradient, lung compliance, shunt, and dead space were determined four times perioperatively. Postoperative tracheal extubation was accomplished at the earliest appropriate time. Both groups exhibited significant postoperative increases in A-a oxygen gradient and shunt (P < 0.000001 for each group) and significant postoperative decreases in dynamic lung compliance (P < 0.000001 for each group). Patients in Group MP exhibited significantly larger increases in postoperative A-a oxygen gradient (P = 0.001) and shunt (P = 0.001) compared with patients in Group NS. Postoperative alterations in dynamic lung compliance, static lung compliance, and dead space were not statistically significant between the groups. The time to postoperative tracheal extubation was prolonged in Group MP patients compared with Group NS patients (769 +/- 294 vs 604 +/- 315 min, respectively; P = 0.05). Methylprednisolone was associated with larger increases in postoperative A-a oxygen gradient and shunt, was unable to prevent postoperative decreases in lung compliance, and prolonged extubation time, which indicate that use of the drug may hinder early tracheal extubation in patients after cardiac surgery. Implications: Traditionally, methylprednisolone has been administered to patients undergoing cardiac surgery to decrease postoperative pulmonary dysfunction. This study revealed that the drug is associated with larger increases in postoperative alveolar-arterial oxygen gradient and shunt and prolonged tracheal extubation time in patients undergoing coronary artery bypass grafting, which indicate that use of the drug may hinder early tracheal extubation. The prevalence of asthma has increased in recent years and depression is common in this population. Minimal data are available on the treatment of depressed asthma patients.
                Ninety adults with asthma and current major depressive disorder were randomized to receive citalopram or placebo for 12 weeks. At each visit, the Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology - Self-Report, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire were administered, and oral corticosteroid use assessed.
                In the evaluable sample (n = 82), the primary outcome, a random regression analysis of HRSD scores, revealed no significant between-group differences. Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6. Changes in asthma symptoms were similar between groups. The groups had similar rates of oral corticosteroid use at baseline, but the citalopram group had less corticosteroid use during the study. Changes in asthma symptom severity correlated with changes in depressive symptom severity.
                A reduction in depressive symptoms was associated with improvement in asthma. Corticosteroid use, an important measure of severe asthma exacerbations, was lower in the citalopram group. Larger clinical trials in this population are warranted. Randomized, controlled trial data from the Heart and Estrogen-progestin Replacement Study were used to evaluate the effect of estrogen plus progestin use on all-cause mortality in women with heart failure and coronary disease. Over the 4.1-year follow-up, estrogen plus progestin use had no effect on all-cause mortality (hazard ratio 1.0, 95% confidence interval 0.7 to 1.4, p = 0.8) in women with heart failure and coronary disease. Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.
                Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.
                Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.
                In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible. Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment. The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid.
                The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and "rescue" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded.
                There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the "trial of steroid" was 0% and 81.3% for positive and negative outcomes respectively.
                Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a "trial of steroid" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.
                In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.
                Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group.
                The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease. The aim was to investigate the health impact of nasal polyposis with asthma and to study effects of endoscopic sinus surgery (ESS), and addition of fluticasone propionate nasal drops (FPND), on health related quality of life (HRQoL).
                Prospective study of 68 patients with nasal polyposis and asthma. Effects were measured with Study 36-Item Short Form (SF-36). A randomized, double-blind, placebo-controlled 14-weeks phase measuring additive effects of FPND 400 µg twice daily (b.i.d.) was included.
                HRQoL was significantly decreased in both Physical Component Summary, PCS, (45 vs 48, p=0.049) and Mental Component Summary, MCS, (43 vs 51, p<0.001) vs reference population. ESS significantly improved PCS, (p=0.027) and MCS (p=0.021) after five weeks. We found significant additional benefit of FPND on three domains (RP, p=0.002; VT, p=0.007; SF, p=0.002). The increase in HRQoL with FPND reached reference population levels in all domains, as well as in both PCS (50, p=0.003) and MCS (52, p=0.002), five weeks after ESS.
                FPND 400 µg b.i.d. can be added to ESS in order to improve, and to reach population levels of, HRQoL already five weeks post-ESS. Physicians should evaluate HRQoL and consider ESS with nasal steroids early in their treatment of these patients.
This meta-analysis showed no beneficial effect of corticosteroid use on mortality, cardiac and pulmonary complications in cardiac surgery patients.