Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.
Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis.
                This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis.
                IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months. 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. 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. 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. To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.
                Randomized, double-blind, placebo-controlled trial.
                ICUs of five hospitals in Memphis.
                Ninety-one patients with severe early ARDS (</= 72 h), 66% with sepsis.
                Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.
                The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.
                In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.
                Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay.
There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.