Spironolactone and colitis: Increased mortality in rodents and in humans

Background: Crohn's disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation. Methods: In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF‐β)‐stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation‐induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results: Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n = 390 deaths, P < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51–2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50–2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82–2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use. Conclusions: We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2‐fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S. (Inflamm Bowel Dis 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92045/1/21929_ftp.pd

Pathogenesis, diagnosis and management of pneumorrhachis

Pneumorrhachis (PR), the presence of intraspinal air, is an exceptional but eminent radiographic finding, accompanied by different aetiologies and possible pathways of air entry into the spinal canal. By reviewing the literature and analysing a personal case of traumatic cervical PR after head injury, we present current data regarding the pathoanatomy, clinical and radiological presentation, diagnosis and differential diagnosis and treatment modalities of patients with PR and associated pathologies to highlight this uncommon phenomenon and outline aetiology-based guidelines for the practical management of PR. Air within the spinal canal can be divided into primary and secondary PR, descriptively classified into extra- or intradural PR and aetiologically subsumed into iatrogenic, traumatic and nontraumatic PR. Intraspinal air is usually found isolated not only in the cervical, thoracic and, less frequently, the lumbosacral regions but can also be located in the entire spinal canal. PR is almost exceptional associated with further air distributions in the body. The pathogenesis and aetiologies of PR are multifold and can be a diagnostic challenge. The diagnostic procedure should include spinal CT, the imaging tool of choice. PR has to be differentiated from free intraspinal gas collections and the coexistence of air and gas within the spinal canal has to be considered differential diagnostically. PR usually represents an asymptomatic epiphenomenon but can also be symptomatic by itself as well as by its underlying pathology. The latter, although often severe, might be concealed and has to be examined carefully to enable adequate patient treatment. The management of PR has to be individualized and frequently requires a multidisciplinary regime

From System to Local to System: Design principles to scale for a system in transition

Societal transitions require the activities of multiple stakeholders on different systemic levels. Designers and design researchers are often involved in supporting specific interventions and sometimes in enabling and facilitating entire processes. Practices and literature in ‘co-creation ecosystems’ are a developing field for them to discuss differences and relatedness of micro-, meso- and macro perspectives. Using the case of a three-year multi-stakeholder co-creation project in the retail industry, the paper analyses processes and principles for making an impact in design-led transition projects. A transition process with three phases is constructed and four principles for making an impact at the various levels were found. Comparing findings with the UK Design Council’s ‘Systemic Design Framework’, the paper suggests process adaptations to scale between the local and the sector/national level. It also contributes to a better understanding of systemic design principles such as Leadership, Storytelling and Systems Thinking

Improvement of developmental outcome between 24 and 36 months corrected age in very preterm infants

Aim: To study early developmental course in preschool-aged very preterm infants and its association with perinatal risk factors and test-taking behaviour. Methods: Children born <30 weeks gestation and/or <1000 g in the Academic Medical Center of Amsterdam were assessed at 24 and 36 months corrected age with the Dutch Bayley Scales of Infant Development-II (BSID-II-NL) and neurological examination. Linear regression analyses for developmental change were performed with perinatal risk factors. Results: One hundred and forty-six children, mean GA 28 weeks and mean birth weight 1043 g, participated. Mental and psychomotor scores improved significantly with 6 and 7 points, respectively, from 24 to 36 months (p <0.01). Mild to severe problems on at least one domain occurred less often at 36 (32%) compared to 24 months (63%) (p <0.01), using corrected scores. Mental improvement was associated with being born very small for gestational age or <28 weeks; psychomotor improvement was associated with not being treated with indomethacin. Difficult test behaviour occurred mostly at 24 months and was associated with non-optimal development at 36 months. Conclusion: Improved developmental outcome and test behaviour were found at 36 compared to 24 months in a cohort of very preterm children. Long-term outcome studies and retesting of behaviourally difficult children are recommende

Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis: Lancet Infectious Diseases

Background Antimicrobial stewardship is advocated to improve the quality of antimicrobial use. We did a systematic review and meta-analysis to assess whether antimicrobial stewardship objectives had any effects in hospitals and long-term care facilities on four predefined patients' outcomes: clinical outcomes, adverse events, costs, and bacterial resistance rates. Methods We identified 14 stewardship objectives and did a separate systematic search for articles relating to each one in Embase, Ovid MEDLINE, and PubMed. Studies were included if they reported data on any of the four predefined outcomes in patients in whom the specific antimicrobial stewardship objective was assessed and compared the findings in patients in whom the objective was or was not met. We used a random-effects model to calculate relative risk reductions with relative risks and 95% CIs. Findings We identified 145 unique studies with data on nine stewardship objectives. Overall, the quality of evidence was generally low and heterogeneity between studies was mostly moderate to high. For the objectives empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation the overall evidence showed significant benefits for one or more of the four outcomes. Guideline-adherent empirical therapy was associated with a relative risk reduction for mortality of 35% (relative risk 0.65, 95% CI 0.54-0.80,