Background
Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this ...study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries.
Methods
Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups.
Results
Ninety‐seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2‐receptor antagonists were used 31% (30/97) of the units. Twenty‐three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP.
Conclusions
In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.
Toll-like receptors (TLRs) are structurally and functionally related and play important roles in the innate and adaptive immune system. By genome scanning, evidence of linkage between chromosome Xp22 ...and asthma and related atopic disorders has previously been obtained. Xp22 harbours the TLR7 and TLR8 genes.
The involvement of TLR7 and TLR8 in the aetiology of asthma and related disorders was investigated by a family based association analysis of two independently ascertained family samples comprising 540 and 424 individuals from 135 and 100 families, respectively. Ten affected individuals from families showing evidence of linkage to Xp22 were screened for sequence variations in TLR7 and 8, and nine single nucleotide polymorphisms (SNPs) identified were tested for association.
In both samples, significant associations were observed for single SNPs and haplotypes of both TLR7 and 8 in all four phenotypes investigated: asthma, rhinitis, atopic dermatitis and increased specific IgE. The most significant association was seen for rs2407992 (TLR8) in asthma (p = 0.00023, sample A and B combined, recessive model). In TLR7, rs179008 showed the strongest association. Both rs179008 and rs2407992 are of putative functional significance, potentially affecting TLR7 processing and TLR8 splicing, respectively. Haplotypes comprising the major alleles of these two SNPs were overtransmitted to the affected offspring (eg, p = 0.00012 in asthma, combined sample, additive model).
The results provide strong evidence that TLR7 and 8 may confer susceptibility to asthma and related atopic disorders and highlight these receptors as interesting targets for individualised, causally directed treatment.
Arthroscopic assessment of articular tissues is highly subjective and poorly reproducible. To ensure optimal patient care, quantitative techniques (e.g., near infrared spectroscopy (NIRS)) could ...substantially enhance arthroscopic diagnosis of initial signs of post-traumatic osteoarthritis (PTOA). Here, we demonstrate, for the first time, the potential of arthroscopic NIRS to simultaneously monitor progressive degeneration of cartilage and subchondral bone in vivo in Shetland ponies undergoing different experimental cartilage repair procedures. Osteochondral tissues adjacent to the repair sites were evaluated using an arthroscopic NIRS probe and significant (p < 0.05) degenerative changes were observed in the tissue properties when compared with tissues from healthy joints. Artificial neural networks (ANN) enabled reliable (ρ = 0.63-0.87, NMRSE = 8.5-17.2%, RPIQ = 1.93-3.03) estimation of articular cartilage biomechanical properties, subchondral bone plate thickness and bone mineral density (BMD), and subchondral trabecular bone thickness, bone volume fraction (BV), BMD, and structure model index (SMI) from in vitro spectral data. The trained ANNs also reliably predicted the properties of an independent in vitro test group (ρ = 0.54-0.91, NMRSE = 5.9-17.6%, RPIQ = 1.68-3.36). However, predictions based on arthroscopic NIR spectra were less reliable (ρ = 0.27-0.74, NMRSE = 14.5-24.0%, RPIQ = 1.35-1.70), possibly due to errors introduced during arthroscopic spectral acquisition. Adaptation of NIRS could address the limitations of conventional arthroscopy through quantitative assessment of lesion severity and extent, thereby enhancing detection of initial signs of PTOA. This would be of high clinical significance, for example, when conducting orthopaedic repair surgeries.
Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post‐traumatic osteoarthritis (PTOA). This study aimed to investigate the ...feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age‐matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included T1, T2, continuous‐wave T1ρ (CWT1ρ), adiabatic T1ρ (AdT1ρ), and T2ρ (AdT2ρ) and relaxation along a fictitious field (TRAFF). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full‐thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T1, CWT1ρ, and AdT1ρ in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT1ρ was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin‐locking amplitudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters (ρ = −0.531 to −0.757). T1, low spin‐lock amplitude CWT1ρ, and AdT1ρ were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T1, CWT1ρ, and AdT1ρ in evaluation of compositional and structural changes in cartilage.
Summary Background Data for the causes of maternal deaths are needed to inform policies to improve maternal health. We developed and analysed global, regional, and subregional estimates of the causes ...of maternal death during 2003–09, with a novel method, updating the previous WHO systematic review. Methods We searched specialised and general bibliographic databases for articles published between between Jan 1, 2003, and Dec 31, 2012, for research data, with no language restrictions, and the WHO mortality database for vital registration data. On the basis of prespecified inclusion criteria, we analysed causes of maternal death from datasets. We aggregated country level estimates to report estimates of causes of death by Millennium Development Goal regions and worldwide, for main and subcauses of death categories with a Bayesian hierarchical model. Findings We identified 23 eligible studies (published 2003–12). We included 417 datasets from 115 countries comprising 60 799 deaths in the analysis. About 73% (1 771 000 of 2 443 000) of all maternal deaths between 2003 and 2009 were due to direct obstetric causes and deaths due to indirect causes accounted for 27·5% (672 000, 95% UI 19·7–37·5) of all deaths. Haemorrhage accounted for 27·1% (661 000, 19·9–36·2), hypertensive disorders 14·0% (343 000, 11·1–17·4), and sepsis 10·7% (261 000, 5·9–18·6) of maternal deaths. The rest of deaths were due to abortion (7·9% 193 000, 4·7–13·2), embolism (3·2% 78 000, 1·8–5·5), and all other direct causes of death (9·6% 235 000, 6·5–14·3). Regional estimates varied substantially. Interpretation Between 2003 and 2009, haemorrhage, hypertensive disorders, and sepsis were responsible for more than half of maternal deaths worldwide. More than a quarter of deaths were attributable to indirect causes. These analyses should inform the prioritisation of health policies, programmes, and funding to reduce maternal deaths at regional and global levels. Further efforts are needed to improve the availability and quality of data related to maternal mortality. Funding USAID, the US Fund for UNICEF through a grant from the Bill & Melinda Gates Foundation to CHERG, and The UNDP/UNFPA/UNICEF/WHO/The World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research.
Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic ...anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA.
Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS.
Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = −0.37, p = 0.03). Overall, n-VNS was well tolerated.
Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.
Long-duration γ-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not ...hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes-analogues of GRBs, but with lower luminosities and fewer γ-rays-can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.
The vagus nerve is a central component of cholinergic anti‐inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t‐VNS) on validated ...parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t‐VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor‐α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t‐VNS exerts an autonomic and a subtle antitumor necrosis factor‐α effect, which warrants further evaluation in larger controlled studies.
In healthy humans, we found that transcutaneous electrical vagal nerve stimulation increases cardiac vagal tone and decreases tumor necrosis factor‐alpha. These preliminary findings warrant further investigation in patients with immune mediated inflammatory disorders such as inflammatory bowel disease.
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Summary
Background
Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma.
Objective
We sought to identify variation in genes with known antiviral and ...pro‐inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus‐induced exacerbations during the peak fall season.
Methods
The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus‐induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study.
Results
A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus‐induced wheezing phenotypes in the COAST study.
Conclusions
We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus‐induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus‐induced exacerbations of asthma.
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