a prospective ‘before/after’ cohort study

Objectives Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long- term effects after implementation of a CDSS. Design This prospective ‘before/after’ cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. Setting Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. Participants Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12 965 ICU days. Intervention Implementation of a CDSS. Outcome measures The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. Main results Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). Conclusions Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU—An International, Prospective, Bi-Center Observational Study (IDeAS)

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs

Exploring the potential of Google Earth as a communication and engagement tool in collaborative Natural Flood Management planning

This paper considers the development and evaluation of a Google Earth “virtual globe” tour for communicating spatial data and engaging stakeholders in the early stages of a natural flood management (NFM) planning scenario, using a rural UK river catchment that suffered significant flooding in 2007. With a range of diverse stakeholder interests to consider, early engagement and the development of trust before decision‐making are essential for the long‐term success of such catchment‐wide projects. A local catchment group was consulted to identify key information requirements, and from this a “virtual globe” tour was created. The process involved specialist skills and expert leadership, but the end result was accessible to a range of audiences. User evaluation indicated that it was easy to navigate and can be used to stimulate interest and engage stakeholders. Participants trusted the content and valued the interactivity of the tour. It was helpful for communicating and educating participants about the catchment, the issues it faces, and the potential to incorporate NFM, particularly for those with little or no prior knowledge. More abstract information was harder to convey and there were limitations in the availability of suitable data for some variables and the in quality of satellite imagery. This exploratory research found that a Google Earth “virtual globe” tour can be a valuable tool in the initial stages of an NFM project, but there are also opportunities to use this technique in the more advanced stages of the planning process. The approach could be used as part of a wider toolkit for communication and engagement and has potential as a decision support tool in other environmental management scenarios with requirements for public participation, enabling the views of a range of participants to be captured through online distribution and to generate discussion in workshop setting

Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719

Enzymatically crosslinked Tyramine-Gellan gum hydrogels as drug delivery system for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint synovial inflammation, as well as cartilage and bone tissue destruction. Current strategies for the treatment of RA can reduce joint inflammation, but the treatment options still represent stability concerns since they are not sufficient and present a fast clearing. Thus, several drug delivery systems (DDS) have been advanced to tackle this limitation. Injectable gellan gum (GG) hydrogels, reduced by physical crosslinking methods, also being proposed as DDS, but this kind of crosslinking can produce hydrogels that become weaker in physiological conditions. Nevertheless, enzymatic crosslinking emerged as an alternative to increase mechanical strength, which can be adjusted by the degree of enzymatic crosslinking. In this study, tyramine-modified gellan gum (Ty-GG) hydrogels were developed via horseradish peroxidase (HRP) crosslinking; and betamethasone was encapsulated within, to increase the specificity and safety in the treatment of patients with RA. Physicochemical results showed that it was possible to modify GG with tyramine, with a degree of substitution of approximately 30%. They showed high mechanical strength and resistance, presenting a controlled betamethasone release profile over time. Ty-GG hydrogels also exhibited no cytotoxic effects and do not negatively affected the metabolic activity and proliferation of chondrogenic primary cells. Furthermore, the main goal was achieved since betamethasone-loaded Ty-GG hydrogels demonstrated to have a more effective therapeutic effect when compared with the administration of betamethasone alone. Therefore, the developed Ty-GG hydrogels represent a promising DDS and a reliable alternative to traditional treatments in patients with RANorte2020 project (“NORTE-08-5369-FSE-000044”), REMIX project (G.A. 778078 — REMIX — H2020-MSCA-RISE-2017), and Gilson Lab, Chonbuk National University, Republic of Korea. The FCT distinction attributed to J. Miguel Oliveira under the Investigator FCT program (IF/01285/2015) is also greatly acknowledged. C. Gonçalves also wish to acknowledge FCT for supporting her research (No. SFRH/BPD/94277/2013

Pain, depression, and quality of life in neuromyelitis optica spectrum disorder: a cross-sectional study of 166 AQP4 antibody-seropositive patients

OBJECTIVES: To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort. METHODS: We included 166 patients with aquaporin-4–seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief Pain Inventory, Beck Depression Inventory–II, and Short Form 36 Health Survey. RESULTS: One hundred twenty-five (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR = 1.27, p = 0.018) and involved upper thoracic segments (OR = 1.31, p = 0.018) were the only predictive factors for chronic pain. The latter was specifically associated with spasticity-associated pain (OR = 1.36, p = 0.002). More than a third (39.8%) suffered from depression, which was moderate to severe in 51.5%. Pain severity (OR = 1.81, p < 0.001) and especially neuropathic character (OR = 3.44, p < 0.001) were associated with depression. Pain severity and walking impairment explained 53.9% of the physical QoL variability, while depression and walking impairment 39.7% of the mental QoL variability. No specific medication was given to 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain. Two-thirds (64.2%) of patients with symptomatic treatment still reported moderate to severe pain. CONCLUSIONS: Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice