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.     

Can corticosteroids be beaten in future asthma therapy?

Despite the enormous therapeutic advance, there is a general trend towards increasing morbidity and mortality due to asthma, which suggests that there is a need for new and improved treatments. The past decade was determined by the so-called "new biology" that identified and cloned almost all receptors and ion channels. This scientific revolution should lead to a more rapid identification of novel targets for major diseases and processes like high throughput screening and combinatorial chemistry should have improved and fastened the development of new drugs. Interestingly, exactly the opposite has happened. With the exception of leukotriene receptor antagonists and some monoclonal antibodies, no new developments have been introduced into asthma therapy during the last decade. The most promising approach is still to find drugs like corticosteroids with multiple functions. However, there is no evidence at the very moment that corticosteroids can be beaten in the next ten years. Therefore, our task is to improve the corticosteroids and make therapy with them even safer. The so-called soft-steroids such as loteprednol and etiprednol belong to the future promising therapeutically effective and safe treatments of allergic disorders.     

Do stimulants improve functioning in adults with ADHD?: A review of the literature

ADHD is prevalent in adulthood and stimulant pharmacotherapy is the primary treatment for uncomplicated presentations. ADHD is associated with significant functional impairment in major life roles. Measurement of the efficacy of stimulant treatment for adult ADHD therefore should include assessment of improvement in role function. A literature search was conducted to identify studies that measured change in function with stimulant treatment in adult ADHD using measures other than global clinical impression or global assessment of function ratings. Five studies were identified that met our search criteria. Evidence of functional improvement with stimulant treatment was found with the following validated self-report measures of functional wellbeing employed across these studies: the Medical Outcome Study 36-item Short Form Health Survey; ADHD Impact Module for Adults; Quality of Life Enjoyment and Satisfaction scale—Short Form; Sheehan Disability Scale, and Social Adjustment Scale—Self-Report. We conclude that investigations using self-report scales provide evidence that stimulant treatment translates into measurable improvement in daily function for adults with ADHD. Further investigation could better characterize the mediators and moderators of individual improvement, an important step towards the personalization of treatment for ADHD in adulthood.     

Plasma concentration monitoring of busulfan: does it improve clinical outcome?

High dosage busulfan (1 mg/kg orally every 6 hours x 16 doses) is frequently used in preparative regimens for haemopoietic stem cell transplantation (HSCT). Busulfan is well absorbed after oral administration, exhibits low protein binding and is metabolised through conjugation with glutathione to form a thiophenium ion. At a given dose, there is considerable variability in the systemic exposure of busulfan, typically expressed as area under the plasma concentration-time curve (AUC) or average concentration at steady state (Css). Relative to that in adolescents and adults, patients less than 4 years of age have an increased apparent oral clearance (CL/F) of busulfan and a higher conjugation rate of busulfan with glutathione in the enterocyte. Several investigators have identified relationships between busulfan Css and outcome in patients undergoing HSCT. Busulfan concentration-response relationships are regimen-, age- and disease-dependent. The busulfan/cyclophosphamide (BU/CY) regimen is the only regimen for which substantial concentration-outcome data exist. Generally, the risk of hepatic veno-occlusive disease is increased with busulfan Css > 900 microg/L. The impact of busulfan Css on veno-occlusive disease may be influenced by the age of the patient and the dose of cyclophosphamide. Lower rates of relapse in chronic myelogenous leukaemia occur in patients with a busulfan Css > 917 microg/L without an increased risk of toxicity. Busulfan Css is also related to the engraftment rate in children, and escalating busulfan doses to achieve a target Css > 600 microg/L improves graft retention. Therapeutic drug monitoring of busulfan should be performed to maximise the likelihood of engraftment and minimise the risk of toxicity and relapse in HSCT patients receiving the BU/CY preparative regimen.     

Therapeutic drug monitoring of mycophenolic acid: does it improve patient outcome?

Treatment with the immunosuppressive agent mycophenolate mofetil (MMF) decreases the risk of rejection after renal transplantation and improves graft survival compared with azathioprine. The exposure to the active metabolite mycophenolic acid (MPA) is correlated to the risk of developing acute rejection. The interpatient variability in exposure of MPA is wide relative to the proposed therapeutic window of the MPA AUC(0 12) (30 - 60 mg.h/l). The pharmacokinetics of MPA are influenced by patient characteristics such as gender, time after transplantation, serum albumin concentration, renal function, comedication and pharmacogenetic factors. Therapeutic drug monitoring is likely to reduce inter-patient variability. Limited sampling strategies are used to predict the full AUC(0 12). Three prospective randomised studies compared concentration controlled MMF therapy to a fixed-dose regimen. Preliminary outcomes of these studies showed conflicting results and longer follow up is needed to further clarify the role of therapeutic drug monitoring in increasing the therapeutic potential of MMF.     

Inhaled corticosteroids in COPD: systemic effects of a local therapy?

Background: There are few data on the effects of inhaled corticosteroids on systemic inflammation in chronic obstructive pulmonary disease (COPD). Objective: Evaluation of the systemic anti-inflammatory effects of inhaled corticosteroids alone or in combination with long acting beta2-agonists. Methods: Analysis of the results of a randomized study assessing the short-term effects of inhaled fluticasone propionate, inhaled fluticasone + salmeterol and placebo on three inflammation biomarkers represented by C-reactive protein, IL-6 and surfactant protein-D. Results/conclusions: Inhaled corticosteroids alone or in combination exhibited partial systemic anti-inflammatory effects, reducing significantly only SP-D serum levels. Further evaluation of effects of inhaled corticosteroids on various biomarkers of systemic inflammation is required in more severe stable COPD.     

Is there a role for inhaled corticosteroids and macrolide therapy in bronchiectasis?

Bronchiectasis is characterised by permanent dilatation of the bronchi that arises from chronic inflammation predominantly caused by bacterial infection. This condition remains a major cause of excess respiratory morbidity and treatment is generally only partly successful. There is an urgent need for improved anti-inflammatory medication to treat bronchiectasis. Two potentially useful therapies are inhaled corticosteroids (ICS) and macrolides. The clinical trials that have been performed in bronchiectasis with these two medications can be considered to be preliminary data. This article reviews the anti-inflammatory properties, clinical efficacy and adverse effects of ICS and macrolides.ICS have a large number of potent anti-inflammatory properties. ICS remain the first-line treatment in asthma, reduce exacerbations in chronic obstructive pulmonary disease, and may improve lung function and symptoms in cystic fibrosis (CF). Four small clinical trials have assessed the effect of high-dose ICS on bronchiectasis. The main reported effect of these trials was a reduction in sputum volume and this may be a marker of decreased airway inflammation. Other possible benefits included decreased cough and sputum inflammatory cells/biomarkers. ICS have a relatively high prevalence of local adverse effects, and may be associated with ocular complications and osteoporosis. These adverse effects can be minimised by prescribing low doses of the medication.Macrolides have both antibacterial and immunomodulatory properties. Macrolides have less marked immunosuppressive properties than corticosteroids, and effects include decreasing mucous production, inhibiting virulence factors and biofilm formation of Pseudomonas aeruginosa, decreasing leukocyte numbers and altering inflammatory mediator release. Macrolides have been shown to be extremely effective in the treatment of diffuse panbronchiolitis, improve lung function and symptoms in asthma and CF, and reduce nasal polyps and secretions in sinusitis. Five small clinical trials have assessed the effect of macrolides on bronchiectasis. Reported benefits include reduced sputum volume, improved lung function and better symptom control. Macrolides are generally well tolerated, although they do have a number of drug interactions. There are concerns about the development of resistance, especially to non-tuberculous mycobacteria, with prolonged macrolide use.The evidence available suggests that both medications have a role in the management of bronchiectasis. More definitive trials of ICS and macrolides in bronchiectasis will clarify the likely benefit of these therapies.     

NSAIDs, corticosteroids and atrial fibrillation?

Evidence that a number of drugs can cause atrial fibrillation has been accumulating since the 2000s. A case-control analysis of a UK general medicine database showed statistically significant increases in the risk of chronic atrial fibrillation in patients taking NSAIDs, after as little as one month of treatment. When NSAID treatment lasted more than 30 days, the incidence was 9.4%, versus 4.7% in the control group, corresponding to a relative risk (RR) of 1.57 (95% confidence interval (95% CI): 1.15 to 2.15). Similar results were found in patients with no history of heart failure. A Danish case-control study yielded similar results. In the UK case-control study, a statistically significant increase in the risk of chronic atrial fibrillation was found in patients taking corticosteroids (5% versus 1.4% in the control group, RR=2.5, 95% CI: 1.6 to 4). The risk increased with the dose. Another Danish case-control study showed that hospitalisation for atrial fibrillation or flutter was twice as frequent among patients exposed to corticosteroids. In contrast, trials in which corticosteroids were given shortly after cardiac surgery, a highly specific setting, showed a decreased risk of atrial fibrillation. In practice, the risk of atrial fibrillation should be taken into account before deciding whether or not to prescribe a corticosteroid or an NSAID, especially to a patient with known risk factors for atrial fibrillation. The heart rate of treated patients should be closely monitored.     

Can the practitioner correctly predict outcome in motivational interviewing?

We have examined whether practitioner ratings (immediately post-intervention) or other recorded characteristics of a single-session 1-hour motivational intervention were predictive of 3-month cannabis use outcome. In the context of a cluster randomized trial involving 200 non help-seeking illegal drug users (age range 16-20), 105 were randomized to the intervention, of whom 97 (92%) were interviewed for followup at 3 months, 96 of whom were current cannabis users at study entry. Six intervention characteristics and seven practitioner ratings as well as patterns of self-motivational statements were investigated in relation to substantial change in use, (which was defined as cessation or reduction by more than 50%). Both practitioner ratings post-session, and also the subject's own elicited self-motivational statements, were found to be predictive of outcome 3 months later. The strongest predictor of substantial change, however, was simply whether change had been discussed during the session. On the basis of the above findings, it does indeed appear possible for outcome to be predicted by the motivational interviewing practitioner immediately following delivery of the intervention, on the basis of simple observations and ratings. This area warrants more specific study.     

What do we know about the safety of corticosteroids in rheumatoid arthritis?

Abstract

Background:

Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience.     

Methadone maintenance. Does dose determine differences in outcome?

We conducted a naturalistic study to determine if higher methadone doses were more effective than lower doses in the outcome variables of illicit drug use, treatment retention, missed medication days, and ratings of patient progress by assigned counselor among 265 patients in a Department of Veterans Affairs Methadone Maintenance Treatment Program. Results indicated no significant differences on any outcome variable by methadone dose. However, we found a significant effect by assigned therapist. Some therapists achieved better outcome results on these same variables compared to other assigned therapists independent of dose level. We conclude that, while methadone maintenance dose is an important variable, researchers need to pay more attention to the interpersonal aspects of methadone maintenance treatment.