Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Depression embodied: an ambiguous striving against fading

Although depression is associated to physical discomfort, meanings of the body in depression are rarely addressed in clinical research. Drawing on the concept of the lived body, this study explores depression as an embodied phenomenon. Using a hermeneutic phenomenological approach, the analysis of narrative‐based interviews with 11 depressed adults discloses a thematic structure of an embodied process of an ambiguous striving against fading. Five subthemes elicit different dimensions of this process, interpreted as disabling or enabling: feeling estranged, feeling confined, feeling burdensome, sensing life and seeking belongingness. In relation to clinical practice, we suggest that the interdisciplinary team can focus on enhancing the enabling dimensions, for example through guided physical activities to support the patient to feel more alive, capable and connected. Moreover, we suggest that the treatment process benefits from an increased awareness of the ambiguity in the patient's struggle, acknowledging both destructive and recharging elements of the withdrawing, and the perceived conflict in‐between.     

Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring bla_SHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.     

Immunomodulatory Metabolites Released by the Frog-Killing Fungus Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen.     

Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.