Corticosteroid-treated Group Research Articles

Clinical Features, Outcomes, and Response to Corticosteroid Treatment of Acute Tubulointerstitial Nephritis: A Single-Centre Retrospective Cohort Study in the Czech Republic

Introduction: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. Methods: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. Results: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169–569) µmol/L in the conservatively managed group versus 374 (249–558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). Conclusions: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

Impact of corticosteroid administration on the response of exposed dental pulp to capping with bioactive cements-experimental study on mongrel dogs

BackgroundCorticosteroids are commonly used as a treatment for a variety of pathological conditions, however, systemic corticosteroid administration has adverse effects including impaired immune response and wound healing. Such complications may affect pulp healing after direct pulp capping. The current study evaluated the influence of corticosteroids on the healing ability of exposed dogs’ dental pulps after direct pulp capping (DPC) with bioactive materials.MethodsTen healthy male dogs were assigned randomly into two groups, 5 dogs each: group I represent the control group which did not receive any medication, and group II was given corticosteroid for 45 days before DPC and till the dogs were euthanized (n = 75 teeth for each group). Following mechanical exposure, the pulps were randomly capped with either Ca(OH)2, MTA, or Biodentine. The pulpal tissues’ reaction to the capping materials was evaluated 65 days postoperatively according to the following parameters: calcific bridge formation, pulpal inflammation, pulp necrosis, and bacterial infiltration.ResultsThe corticosteroid-treated group revealed no significant difference compared to the control group concerning the pulp healing response (P > 0.05). Both Biodentine and MTA-treated specimens revealed significant differences with Ca(OH)2-treated specimens (P < 0.05) which displayed a superior positive effect of both MTA and Biodentine to Ca(OH)2 regarding all the parameters.ConclusionsDirect pulp capping technique whenever indicated in subjects treated with corticosteroid immunosuppressive drugs like prednisone performed well in aseptic conditions especially when capped with bioactive materials.

Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections.

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People’s Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.

Effect of corticosteroid therapy in the early phase of acute respiratory distress syndrome: a propensity-matched cohort study.

Background/AimsIt is unclear whether corticosteroid use in patients with acute respiratory distress syndrome (ARDS) improves survival. This study aimed to investigate whether the administration of corticosteroids to patients in the early phase of moderate to severe ARDS is associated with improved outcomes.MethodsWe analyzed the data of patients who received corticosteroids within 7 days of the onset of ARDS between June 2006 and December 2015 at a single tertiary teaching hospital. A total of 565 patients admitted with moderate to severe ARDS were eligible. The outcomes of patients treated with methylprednisolone 40 to 180 mg/day or equivalent (n = 404) were compared to those who did not receive steroids (n = 161). The primary and secondary outcomes were 28- and 90-day mortality rates, respectively. Propensity scores were used to adjust for baseline covariates.ResultsThe overall mortality at 28 days was not significantly different between the corticosteroid-treated and control groups (43.8% vs. 41%, p = 0.541). At 90 days, the overall mortality rate was higher in the corticosteroid-treated group than in the control group (59.2% vs. 48.4%, p = 0.021). However, on propensity score matching, corticosteroid therapy was not associated with a higher 28-day mortality rate (odds ratio, 1.031; 95% confidence interval, 0.657 to 1.618; p = 0.895) and 90 days (odds ratio, 1.435; 95% confidence interval, 0.877 to 2.348; p = 0.151).ConclusionsCorticosteroid therapy was not associated with 28- or 90-day mortality in the early phase of moderate to severe ARDS on propensity score matching analysis.

A Lille model for predicting the response of severe alcoholic hepatitis to corticosteroid treatment in Japanese patients.

Corticosteroids are the most widely used agents for the treatment of severe alcoholic hepatitis (SAH). The therapeutic effectiveness of corticosteroids is assessed by the Lille model, which has been validated well in patient cohorts in North America and Europe; however, its usefulness has not yet been confirmed independently in Japanese patients. The present study aimed to determine whether the Lille model could predict the prognosis of SAH in Japanese patients. This was a retrospective cohort study including 32 SAH patients who were admitted to our institute from April 2011 to February 2018. According to the previously validated Lille model cut-off value, patients who received corticosteroids were classified as corticosteroid responders or non-responders (with responders obtaining a Lille score ≥ 0.45), followed by assessment for the 6-month prognosis. Out of 32 patients, 26 were treated with corticosteroids. The 28-day and 6-month mortality rates in the corticosteroid-treated group were 23.1% and 46.2%, respectively. The median Lille score was significantly higher in patients who died or underwent liver transplantation (0.647) than in those who survived without undergoing transplantation (0.226; P < 0.0182). The 6-month transplant-free survival rate of non-responders (Lille score ≥ 0.45) was significantly lower (27.3%; 95% confidence interval, 9.0-58.6%) than that of responders (Lille score < 0.45, 73.3%; 95% confidence interval, 46.7-90.0%; P = 0.0149, log-rank test). The Lille score could be useful for predicting the 6-month prognosis of Japanese SAH patients after corticosteroid therapy.

A model of pulmonary toxoplasmosis in rats as potential impact on immune deficient diseases

Toxoplasma gondii is an obligate intracellular zoonotic protozoan. Pulmonary involvement is common in immunocompromised hosts but rarely occurs in immunocompetent ones. Rat pulmonary involvement could be considered as a good representative model for study of human toxoplasmosis infection to either acute toxoplasmosis, chronic toxoplasmosis, or disseminated toxoplasmosis in human immunodeficiency virus (HIV) patients. Forty Swiss-Webster rats were divided into four groups each ten rats: group 1, non-infected and untreated (normal); group 2, acute infected non-treated; and groups 3 and 4, chronic infected non-treated and corticosteroid treated respectively. Lung tissue and blood samples were taken during acute and chronic stages for parasitological and histopathological study and serological assay. Acute and chronic states revealed the presence of viable toxoplasma tachyzoites and bradyzoites in lung tissue respectively. Serological assay showed different results in acute and chronic infections. The histopathological changes in acute rat group showed that per alveolar septa has been swollen due to swelling of the pneumocystis type I and II and the lining cells of the alveoli became low cuboidal in shape. The histopathological changes in chronic untreated rat group showed that the majority of alveolar walls were thickened due to swelling of the alveolar epithelial cells and mononuclear inflammatory cells and the bronchioles due to hyperplasia of its lining epithelium. Some of the blood vessel wall contained large number of chronic Toxoplasma cysts and surrounded by mononuclear cells. While chronic corticosteroid-treated rat group showed perivascular and alveolar edema with congested per alveolar blood capillaries and alveolar edema with compensatory emphysema of some others. The study concluded that toxoplasmosis is a great of interest, serious, and often a life-threatening disease in immune-deficient patients and sometimes in immunocompetent ones. Pulmonary toxoplasmosis should be considered in the differential diagnosis in potentially HIV-infected patients with respiratory symptoms and bilateral pulmonary infiltrates. Early diagnosis and initiating specific good therapy is essential.

The Management of Autoimmune Hepatitis Patients with Decompensated Cirrhosis: Real-World Experience and a Comprehensive Review.

There is a paucity of information related to the usefulness of corticosteroid therapy in autoimmune hepatitis (AIH) with decompensated cirrhosis. In this study, we sought to determine the therapeutic effect of corticosteroids in this special group of AIH patients. Eighty-two AIH patients with decompensated cirrhosis were included through a retrospective analysis from January 2009 to September 2015. Sixty-four patients were treated with corticosteroids while 18 patients did not receive any corticosteroids. Clinical, laboratory, and histological characteristics and outcomes were analyzed comparing corticosteroid-treated and untreated groups. Patients that did not receive corticosteroids were older than corticosteroid-treated patients and had a worse survival. In corticosteroid-treated group, 40 of 64 patients reverted to compensated state and 15 patients remained decompensated, while 9 patients experienced liver-related death or transplantation. Patients who reverted to compensated state had significantly greater ALT, AST, GGT, white blood cell count, and platelet levels at presentation. Changes (Δ) in total bilirubin (TBIL) and MELD scores at day 7 after starting corticosteroid therapy revealed favorable predictive effects of treatment outcomes. Survival was significantly greater in patients with a ΔTBIL <-0.196mg/dL (p = 0.001) 7days after treatment. Infection was the most common cause of death or transplantation in the patients with treatment failure. Although it cannot be determined whether the results were due to the therapy or underlying patient characteristics, survival was greater in the corticosteroid-treated group with the benefit being greatest in patients with the greatest decrease in TBIL at day 7 after starting corticosteroid therapy.

Betamethasone and dexamethasone in adult community-acquired bacterial meningitis: a quality registry study from 1995 to 2014

Acute bacterial meningitis (ABM) is a highly lethal disease. Available data support the use of corticosteroids in high-income countries, but the effect on mortality is still controversial. The effects of corticosteroids on mortality and sequelae were evaluated in the national Swedish quality registry. In total, during 1995–2014 1746 adults with ABM were included, of whom 989 were treated with corticosteroids (betamethasone, n = 766; dexamethasone, n = 248; methylprednisolone, n = 2), 498 were not given corticosteroids and in 259 patients data for corticosteroids were missing. Fatal outcome was observed in 8.9% of the patients in the corticosteroid-treated group vs. 17.9% in the non-corticosteroid-treated group (p <0.001), resulting in an odds ratio (OR) of 0.57 with a 95% confidence interval (CI) of 0.40–0.81 adjusted for age, sex, mental status, and door-to-antibiotic time. In patients with meningitis caused by S. pneumoniae, mortality was 10.2% in the corticosteroid-treated group and 21.3% in the non-corticosteroid-treated group (p <0.001) with an adjusted OR of 0.50 (95% CI 0.31–0.80). In ABM patients with non-pneumococcal aetiology the adjusted OR was 0.71 (95% CI 0.40–1.26). Lower mortality was observed in the corticosteroid-treated group with impaired mental status, whereas no significant difference was found in patients with unaffected mental status. The adjusted ORs for betamethasone and dexamethasone were 0.49 (95% CI 0.28–0.84) and 0.61 (95% CI 0.37–1.01), respectively. Corticosteroid treatment decreases mortality in ABM and should be administered initially with antibiotics in adult ABM patients with impaired mental status regardless of presumed aetiology. Betamethasone seems to be at least as effective as dexamethasone.

Safety of Proctocolectomy for Ulcerative Colitis Under Elective and Non-Elective Circumstances: Preoperative Corticosteroid Treatment Worsens Outcome

Background/Aims: Approximately 20% of patients undergoing surgery for ulcerative colitis will retain their rectum. A single-stage proctocolectomy could be an appropriate procedure in patients who are definitely not candidates for a later restorative procedure, but it is generally not advised in acutely ill patients. The aim was to investigate the safety of one-stage proctocolectomy under elective and non-elective circumstances, with specific reference to identifying possible risk factors for postoperative complications. Methods: A retrospective cohort study, including 54 consecutive patients undergoing proctocolectomy for ulcerative colitis. Out of these, 27 (50%) were admitted non-electively. Results: Postoperative complications were observed in 30 patients (54%). Wound dehiscence, wound infection, and impaired perineal wound healing were observed in 10 (18.5%), 8 (14.8%), and 10 (18.5%) of the patients, respectively. There was no difference between elective and non-elective cases. Complications were observed more often in patients receiving high-dose corticosteroids (18/26 vs. 12/28; p = 0.06). Impaired perineal wound healing and reoperations were observed more often in the corticosteroid-treated group (8/26 vs. 2/28; p = 0.04 and 12/26 vs. 1/28; p = 0.0003). Conclusions: Proctocolectomy is equally safe under elective and non-elective situations, but a preoperative treatment with high-dose corticosteroids is associated with an increased risk of complications and reoperations.

Efectos de la Corticoterapia Sistémica Sobre la Densidad Mineral Ósea en Pacientes con Artritis Reumatoide

Se realizó un estudio transversal de tipo casos y controles en 180 pacientes con artritis reumatoide (AR) a quienes se les determinó la densidad mineral ósea (DMO). Los pacientes fueron separados en dos grupos, según recibían o no terapia esteroidea. Fueron excluidos los pacientes con patología concomitante o tratamiento que afecte la DMO. Se controló la edad, raza, sexo, tiempo de enfermedad, uso de metotrexato o calcio, fecha de última regla, capacidad funcional y hábitos nocivos. El grupo de casos incluyó pacientes de 31 - 85 años (promedio 54,6 ± 11,8) que habían recibido prednisona 2,5 - 10 mg/día (5,8 ± 2,0 mg/día) durante 3 - 300 meses (54 ± 71,1 meses). La terapia esteroidea no se asoció con diferencias estadísticamente significativas al comparar la DMO (g/cm2) a nivel de columna lumbar (L2: 0,917 ± 0,173 vs. 0,930 ± 0,162; L3: 0,957 ± 0,187 vs. 0,969 ± 0,170; L4: 0,957 ± 0,187 vs. 0,969 ± 0,170; L2 - L4: 0,937 ± 0,170 vs. 0,956 ± 0,166), cuello de fémur (0,731 ± 0,143 vs. 0,761 ± 0,159) y triángulo de Ward (0,630 ± 0,176 vs. 0,679 ± 0,188). A pesar que se hallaron diferencias a nivel de trocánter (0,617 ± 0,139 vs. 0,672 ± 0,145; p &amp;lt; 0,05), en el análisis de regresión lineal múltiple éstas desaparecieron. Se concluye que en los pacientes con AR estudiados, la DMO no varió significativamente entre quienes recibían terapia esteroidea a dosis bajas y los que no recibieron corticoides.

The impact of early and brief corticosteroids on the clinical course of primary pulmonary coccidioidomycosis

Primary pulmonary coccidioidomycosis can often be associated with hypersensitivity symptoms treatable with a short course of palliative corticosteroids. Long-term use of corticosteroids is a known risk factor for severe or disseminated infection but the effects of short-term use are not known. A retrospective review was conducted of immunocompetent patients with acute pulmonary coccidioidomycosis who received systemic corticosteroids for relief of coccidioidal-related symptoms. Age- and sex-matched controls were also reviewed. Predetermined end-points were assessed. Seventy-four patients met inclusion criteria for the corticosteroid-treated group, and 74 controls were identified. Cumulative corticosteroid (prednisone-equivalent) doses were 10 mg → 3,600 mg (mean = 206 mg; median = 120 mg). Corticosteroids were prescribed most commonly for rash 43/74 [58%] or asthma/wheezing/cough 30/74 [41%]. Coccidioidal-related hospitalization occurred in 19 patients in the corticosteroid group vs. 22 in the control group (P = .58). Coccidioidal-related symptoms resolved within a mean of 19 weeks (median = 8 weeks [range = 2-208 weeks]) vs. 32.3 weeks (median = 8 weeks [range = 1-1040 weeks]) in the corticosteroid and control groups (P = .38). Relapse of symptoms occurred in 12% of both groups (P > .99). Extrapulmonary dissemination occurred in 3% vs. 4.0% (P > .99) in the corticosteroid and control groups, respectively. This study found no adverse effects of short-term corticosteroid therapy for early symptomatic treatment in acute pulmonary coccidioidomycosis.

Prevention of Respiratory Distress Syndrome in Preterm Infants by Antenatal Ambroxol: A Meta-Analysis of Randomized Controlled Trials

To evaluate the efficacy and safety of antenatal ambroxol as a preventive therapeutic of respiratory distress syndrome (RDS) in preterm infants. Randomized controlled trials of antenatal ambroxol treatment for RDS in preterm infants published up to March 2012 were downloaded from the Cochrane Library, PubMed, EMBASE, Science Citation Index, and Google Scholar databases. Data were evaluated for homogeneity and analyzed by the Cochrane Collaboration's RevMan software. Twelve trials involving a total of 1335 premature infants were selected for meta-analysis. Neonatal RDS was lower in the ambroxol-treated group than in the groups treated with placebo (risk ratio [RR] = 0.38, 95% confidence interval [CI]: 0.24 to 0.59) or corticosteroids (RR = 0.49, 95% CI: 0.31 to 0.78). The ambroxol-treated group had lower risk of neonatal infection than the corticosteroid-treated group (RR = 0.36, 95% CI: 0.18 to 0.73). In cases of inevitable preterm birth, antenatal ambroxol is recommended over corticosteroids to prevent neonatal RDS. However, further research is necessary to determine the optimal treatment dosages and regimens of antenatal ambroxol to achieve consistent superior results over corticosteroids.

Differences in Clinical Profile and Relapse Rate of Type 1 Versus Type 2 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.

Histologic Study of Acute Vocal Fold Wound Healing after Corticosteroid Injection in a Rabbit Model

Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects on wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for quantification of collagen deposition. There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collagen deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). The present results suggest that dexamethasone reduces collagen deposition during acute vocal fold wound healing.

New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model

IntroductionAvascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH.MethodsBesides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC).ResultsAlthough rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS control), alpha-2-macroglobulin (A2M) gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly, A2M is known to share vascular, osteogenic and cartilage functions relevant for ANFH.ConclusionsThe findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a potential marker, and a treatment target, for early ANFH should be carried out.

Inhaled Corticosteroids in Patients With Chronic Obstructive Pulmonary Disease

To the Editor: We are concerned about possible data discrepancies in the systematic review and meta-analysis of inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease (COPD) by Dr Drummond and colleagues. In the analysis of pneumonia events from the study by Burge et al, Drummond et al reported 87 of 372 events in the inhaled corticosteroid group vs 101 of 370 events in the control group, reflecting a control event rate that is considerably higher than any other trial in the metaanalysis. However, the trial publication actually reports on “lower respiratory serious adverse events” rather than pneumonia events. The company trial report from the GlaxoSmithKline Clinical Trial Register (FLTB3054, the identification number for the study by Burge et al) shows that there were only 18 and 8 pneumonia events in the fluticasone and control groups, respectively. We believe that a substantial proportion of the lower respiratory serious adverse events data in the trial publication were actually COPD exacerbations. We question the inclusion of the trial by Wedzicha et al in this meta-analysis. For an unconfounded comparison to be possible, Drummond et al should have selected trials in which the sole difference between the intervention arms was the use of an inhaled corticosteroid. In the context of a metaanalysis focusing on inhaled corticosteroids, the study by Wedzicha et al represents a confounded comparison of fluticasone/salmeterol combination vs tiotropium. The corticosteroid-treated group differed in 2 important respects from the control tiotropium arm: patients received an inhaled corticosteroid, and patients received salmeterol. Any differences in relative treatment effect could have arisen from the administration of salmeterol rather than from the inhaled corticosteroid. Finally, for the Calverley et al 2007 trial (reference 12 in the study by Drummond et al), we refer to the updated pneumonia data in the UK Medicines and Healthcare Regulatory Authority safety newsletter. Drummond et al appear to have estimated the number of pneumonia events using the percentage probability of pneumonia (based on KaplanMeier analysis) for this trial. However, the percentage probability of pneumonia does not provide an exact estimate of the absolute event rate for pneumonia, as is apparent from the different figures presented within the regulatory agency document. These issues argue for meta-analysis on adverse effects to include data from clinical trial registries as well as those submitted to regulatory agencies to obtain accurate estimates of risk. Moreover, consistent and clear reporting of adverse events is essential. Resolving these discrepancies in the data are likely to remove the substantial heterogeneity that exists in this meta-analysis of pneumonia.

The Effect of Local Corticosteroid or Ketorolac Exposure on Histologic and Biomechanical Properties of Rabbit Tendon and Cartilage

Tendonitis, tenosynovitis, and the arthritides are clinical problems commonly encountered in daily orthopaedic practice. Systemic anti-inflammatories, physical therapy, and local corticosteroid injections all are used as nonoperative treatments of these conditions. Systemic anti-inflammatory agents and local corticosteroid agents, however, can be associated with adverse effects that render them intolerable to some patients. As a preliminary study assessing the feasibility of local injection of nonsteroidal anti-inflammatory medication, the histological and biomechanical effects of local exposure of rabbit cartilage and tendon to injectable steroidal (corticosteroid) and injectable nonsteroidal anti-inflammatory agents (ketorolac tromethamine, KT) were determined. Thirty rabbits underwent bilateral knee joint, patellar tendon, and Achilles tendon injections with either normal saline, corticosteroid, or KT. Mechanical and histologic evaluation of the tissues was performed at 6 and 15 weeks after injection. Gross tendon adhesions were observed in more corticosteroid-treated specimens than those exposed to normal saline or KT. Microscopic evaluation of tendons revealed no significant differences among the three groups. Mild cartilage degenerative changes were noted across all groups. Evidence of cartilage necrosis was noted for the corticosteroid-treated group only. Tendons exposed to corticosteroid or KT demonstrated increased load and energy to failure, but exhibited no difference in material stiffness or strain. The use of an injectable nonsteroidal anti-inflammatory agent may be safe and even pose less threat to local tissues after intra-articular and peri-tendinous administration.

Do Corticosteroids Prevent Oesophageal Stricture After Corrosive Ingestion?

The most serious complication of corrosive damage to the oesophagus besides perforation is stricture formation. The role of corticosteroids in preventing corrosive-induced strictures is controversial. This review evaluates the usefulness of corticosteroid treatment by critically assessing clinical reports published between 1991 and 2004 in the English, German, French and Spanish literature. Inclusion criteria were the presence of second- or third-degree oesophageal injuries documented by endoscopy and management involving either at least an 8-day course of corticosteroids or no steroid therapy. Ten studies with a total of 572 patients fulfilled the inclusion criteria: six studies employed corticosteroids, two studies did not use corticosteroids, and two studies compared the outcome with and without corticosteroid treatment. In those patients with second-degree burns, the incidence of stricture in the corticosteroid-treated patients was 13.8% and in the non-corticosteroid-treated patients was 6.3%. In those patients with third-degree burns, significantly worse results were found in the corticosteroid-treated group (71.0%) than in the non-corticosteroid-treated group (23.1%). As all studies did not separate second- and third-degree burns, re-analysis of the outcome was undertaken. In the 305 patients treated with corticosteroids, 35.1% developed strictures, whereas 33.3% of the 267 non-corticosteroid-treated patients developed strictures. These data suggest that systemic corticosteroids are not beneficial for second- and third-degree corrosive oesophageal burns. Therefore, the use of corticosteroids in the management of corrosive ingestions should be abandoned as they do not prevent the development of strictures and may lead to the development of serious adverse effects.

Effects of different anti‐asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics

Inhaled corticosteroids, leukotriene receptor antagonists, and theophylline are recommended for the treatment of mild persistent asthma. The aim of this study was to compare the changes in sputum total cell and eosinophil counts, and eosinophil cationic protein (ECP) levels in serum and sputum following treatment with leukotriene receptor antagonists, inhaled corticosteroids, and theophylline in patients with mild persistent asthma. Total cell counts, eosinophil percentage, and ECP levels in induced sputum and serum were determined both before and after treatment. Prior to sputum induction, FEV1 and PEF values and symptom scores were recorded at baseline and after 8 weeks of treatment. After baseline measurements, the asthmatic patients (n = 30) were randomized into three groups. A total of 10 patients were treated with zafirlukast, 20 mg bd, 10 with budesonide inhaler 200 microg bd, and 10 with theophylline 200 mg bd. There were significant decreases in sputum total cell counts and eosinophil percentage in all treatment groups. However, the decrease in sputum eosinophil counts was more significant in the corticosteroid-treated group. Although sputum ECP levels decreased significantly in the groups treated with zafirlukast and budesonide (zafirlukast group, 580-135 microg/L, P < 0.01; budesonide group, 683-268 microg/L, P < 0.01), the decrease was not statistically significant in the theophylline-treated group (498-361 microg/L, P > 0.05). In contrast, there were no significant changes in serum ECP levels in any of the treatment groups. All three treatments resulted in significant decreases in sputum total cell counts and eosinophil percentage, but the decrease in sputum ECP level was only seen in the groups treated with budesonide and zafirlukast. These results suggest that although all three treatments are considered as first-line treatments in most consensuses, theophylline seems to have less of an inhibitory effect on eosinophil activation.

EFFECTS OF MONTELUKAST AND BECLOMETHASONE ON AIRWAY FUNCTION AND ASTHMA CONTROL

Israel E, Chervinsky PS, Friedman B, et al. J Allergy Clin Immunol. 2002;110:847–854The primary objective of asthma therapy is the maintenance of asthma control, and the most common measures of such control in clinical studies reflect pulmonary function; forced expiratory volume in 1 second (FEV1) is often used. The authors sought to use a different parameter, ie, days of asthma control, as the primary measure, because observations regarding the need for both rescue medications and unscheduled asthma-related health care are central to perceived wellness.This multicenter study involved 782 individuals, ≥15 years of age, with a ≥1-year history of moderate persistent asthma (baseline FEV1: 50–85% of predicted values) but no controller therapy at the time of enrollment. All patients were required to have a current daily need for inhaled albuterol and documented airway reversibility of ≥15% at the time of entry.Patients were randomly assigned to receive montelukast (10 mg, each evening), beclomethasone (200 μg, twice daily), or placebo, with a ratio of 3:3:1. The use of spacers was not required. Compliance was monitored with pill counts and simple patient reports of inhaler use. A day of asthma control was defined as a day with no more than 2 puffs of albuterol treatment, no nocturnal awakenings with asthma, and no need for acute medical attention. An asthma exacerbation was defined as ≥3 consecutive days without asthma control. An occurrence of sustained asthma control was defined as ≥3 consecutive days with control. Subjects completed diary cards during the 2-week, single-blind, run-in period and during the 6-week, double-blind, treatment phase. The primary measure was the percentage of days of asthma control during the treatment phase. Secondary measures included average daily albuterol use, percentages of patients with and without attacks, asthma exacerbations, occurrence of sustained asthma control, rescue corticosteroid use, and changes in FEV1 from baseline values. Clinic visits occurred every 3 weeks during the double-blind phase, and spirometry was performed at that time.The mean percentages of days of asthma control for patients who received montelukast or beclomethasone were similar and were significantly better than that for placebo recipients. Both drugs resulted in significant improvements in FEV1, but the benefit was greater with beclomethasone. There was no difference between the active treatment groups in any of the other secondary measures, and both treatments were clearly superior to placebo for most parameters.Montelukast and beclomethasone were of similar efficacy, as judged by indices of clinical control other than FEV1. The latter parameter may underestimate clinical effectiveness.Considering the severity of asthma among these individuals, it might seem surprising that these drugs performed so similarly during the 6-week active treatment phase. One might be tempted to attribute this to presumed poor compliance with the inhaled corticosteroid, compared with the convenient montelukast tablet, especially because beclomethasone monitoring was through reports alone. However, there is no doubt that beclomethasone outperformed the leukotriene receptor antagonist in FEV1 measures, suggesting reasonable compliance and greater potency in improving pulmonary function. Six weeks is probably too short a period to detect differences in major attacks between the 2 treatment groups, and it is likely that a much longer treatment period would have revealed more favorable results for most parameters, including the primary measure, for the inhaled corticosteroid-treated group. Almost by definition, most of these patients had asthma that was too severe to be treated with just 1 drug; a more interesting comparison would have been among patients with mild persistent disease, without histories of hospitalization or recurrent acute attacks.