Inhaled drugs to reduce exacerbations in patients with chronic obstructive pulmonary disease: a network meta-analysis

BACKGROUND: Most patients with chronic obstructive pulmonary disease (COPD) receive inhaled long-acting bronchodilators and inhaled corticosteroids. Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo. However, there are relatively few head-to-head comparisons and conventional meta-analyses focus on single comparisons rather than on a simultaneous analysis of competing drug regimens that would allow rank ordering of their effectiveness. Therefore we assessed, using a networkmeta analytic technique, the relative effectiveness of the common inhaled drug regimes used to reduce exacerbations in patients with COPD. METHODS: We conducted a systematic review and searched existing systematic reviews and electronic databases for randomized trials of >=4 weeks' duration that assessed the effectiveness of inhaled drug regimes on exacerbations in patients with stable COPD. We extracted participants and intervention characteristics from included trials and assessed their methodological quality. For each treatment group we registered the proportion of patients with >=1 exacerbation during follow-up. We used treatment-arm based logistic regression analysis to estimate the absolute and relative effects of inhaled drug treatments while preserving randomization within trials. RESULTS: We identified 35 trials enrolling 26,786 patients with COPD of whom 27% had >=1 exacerbation. All regimes reduced exacerbations statistically significantly compared with placebo (odds ratios ranging from 0.71 (95%confidence interval [CI] 0.64 to 0.80) for long-acting anticholinergics to 0.78 (95% CI 0.70 to 0.86) for inhaled corticosteroids). Compared with long-acting bronchodilators alone, combined treatment was not more effective (comparison with long-acting beta-agonists: odds ratio 0.93 [95% CI 0.84 to 1.04] and comparison with long-acting anticholinergics: odds ratio 1.02 [95% CI 0.90 to 1.16], respectively). If FEV1 was 40% predicted. This effect modification was significant for inhaled corticosteroids (P=0.02 for interaction) and combination treatment (P=0.01) but not for long-acting anticholinergics (P=0.46). A limitation of this analysis is its exclusive focus on exacerbations and lack of FEV1 data for individual patients. CONCLUSIONS: We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations. Inhaled corticosteroids when added to long-acting beta-agonists reduce exacerbations only in patients with COPD with FEV1<=40%

Rational pain management in complex regional pain syndrome 1 (CRPS 1)--a network meta-analysis

OBJECTIVE Guidelines for complex regional pain syndrome (CRPS) 1 advocate several substance classes to reduce pain and support physical rehabilitation, but guidance about which agent should be prioritized when designing a therapeutic regimen is not provided. Using a network meta-analytic approach, we examined the efficacy of all agent classes investigated in randomized clinical trials of CRPS 1 and provide a rank order of various substances stratified by length of illness duration. DESIGN In this study a network meta-analysis was conducted. PATIENTS The participants of this study were patients with CRPS 1. METHOD Searches in electronic, previous systematic reviews, conference abstracts, book chapters, and the reference lists of relevant articles were performed. Eligible studies were randomized controlled trials comparing at least one analgesic agent with placebo or with another analgesic and reporting efficacy in reducing pain. Summary efficacy stratified by symptom duration and length of follow-up was computed across all substance classes. Two authors independently extracted data. RESULTS In total, 16 studies were included in the analysis. Bisphosphonates appear to be the treatment of choice in early stages of CRPS 1. The effects of calcitonin surpass that of bisphosphonates and other substances as a short-term medication in more chronic stages of the illness. While most medications showed some efficacy on short-term follow-up, only bisphosphonates, NMDA analogs, and vasodilators showed better long-term pain reduction than placebo. LIMITATION For some drug classes, only a few studies were available and many studies included a small group of patients. Insufficient data were available to analyze efficacy on disability. CONCLUSION This network meta-analysis indicates that a rational pharmacological treatment strategy of pain management should consider bisphosphonates in early CRPS 1 and a short-term course of calcitonin in later stages. While most medications showed some efficacy on short-term follow-up, only bisphosphonates, NMDA analogs and vasodilators showed better long-term pain reduction than placebo

Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: Network meta-analysis of randomized trials

The efficacies and adverse effects of different antibiotics for uncomplicated urinary tract infections (UTIs) have been studied by standard meta-analytic methods using pairwise direct comparisons of antimicrobial treatments: the effects of one treatment are compared to those of either another treatment or placebo. However, for clinical decisions, we need to know the effectiveness of each possible treatment in comparison with all relevant alternatives, not with just one. To compare the efficacies and adverse effects of all relevant antibiotics for UTI treatment simultaneously by performing a network meta-analysis using direct and indirect treatment comparisons. Using logistic regression analysis, we performed a network meta-analysis of randomized controlled trials (RCTs) published after 1999 that compared different oral antibiotic or placebo regimens for UTI treatment in general practice or outpatient settings. We looked at five binary outcomes: early clinical, early bacteriological, late clinical and late bacteriological outcomes, as well as adverse effects. Consequently, a ranking of the antibiotic regimens could be composed. Using a network structure, we could compare and rank nine treatments from 10 studies. Overall, ciprofloxacin and gatifloxacin appeared the most effective treatments, and amoxicillin-clavulanate appeared the least effective treatment. In terms of adverse effects, there were no significant differences. Network meta-analysis shows some clear efficacy differences between different antibiotic treatments for UTI in women. It provides a useful tool for clinical decision making in everyday practice. Moreover, the method can be used for meta-analyses of RCTs across primary care and beyon

Calcium scores and matrix Gla protein levels: association with vitamin K status

Background Vascular calcification in humans is associated with an increased cardiovascular risk. Carboxylated matrix Gla protein (cMGP) inhibits vascular calcification. Vitamin K is an essential cofactor for the activation of uncarboxylated matrix Gla protein (ucMGP). It has been suggested that patients on long-term treatment with vitamin K antagonists develop aortic valve calcifications because of lower levels of circulating MGP. We therefore hypothesized that arterial calcification and a low vitamin K status are associated with ucMGP. To that aim, we measured arterial calcium scores, the osteocalcin ratio (OCR), as a proxy for vitamin K status, and ucMGP. Materials and methods In 36 hypertensive patients, we determined the Agatston score with computer tomography scans of the abdominal aorta, carotid and coronary arteries. The total calcium score was calculated as the sum of the separate Z-scores. Results The total calcium Z-score was significantly correlated to age (r = 0 center dot 683, P &lt;0 center dot 001), smoking (r = 0 center dot 372, P = 0 center dot 026), total cholesterol (r = 0 center dot 353, P = 0 center dot 034), LDL cholesterol (r = 0 center dot 490, P = 0 center dot 003), triglycerides (r = 0 center dot 506, P = 0 center dot 002), fasting glucose (r = 0 center dot 454, P = 0 center dot 005), systolic blood pressure (r = 0 center dot 363, P = 0 center dot 029) and pulse pressure (r = 0 center dot 685, P &lt;0 center dot 001). In multivariate regression analyses, OCR and total calcium score were significantly associated with ucMGP. Conclusions We found a positive association of total arterial calcium score and a high OCR (reflecting low vitamin K status) with ucMGP serum levels. This warrants further studies to explore the pathophysiological background of this phenomenon

Clinical impact of the use of additional ultrasonography in diagnostic breast imaging.

Item does not contain fulltextThe degree of adherence with evidence-based guidelines for the use of breast ultrasonography was determined in clinical practice of radiologists in six hospitals. Additional ultrasonography was performed in 2,272 (53%) of all 4,257 patients referred for mammography. High adherence rates (mean: 95%) were observed for guidelines recommending ultrasonography in patients referred for palpable breast masses and abnormal screening and diagnostic mammograms. Lower adherence rates (mean: 81%, Pearson correlation coefficient= -0.57; p=0.001) were found for guidelines advising against additional ultrasonography in patients referred for breast symptoms, a known benign abnormality, a family history or anxiety of breast cancer. The overuse of ultrasonography in 442 patients and underuse in 95 patients led to five additional false-positive results. It was concluded that the guidelines seem workable and feasible in clinical practice and that the current daily routine of diagnostic breast imaging corresponded to a great extent to the guidelines proposed