bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial
Authors: Kelly S. J. , Moran J. L. , Williams P. J. , Burns K. , Rowland A. , Miners J. O. , Peake S. L. 
Published: September 2016

SummaryParacetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single‐centre, prospective, open‐label, randomised, parallel‐arm, active‐control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l−1 [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97–8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.
The analgesic efficacy of sciatic nerve block in addition to femoral nerve block in patients undergoing total knee arthroplasty: a systematic review and meta‐analysis
Authors: Grape S. , Kirkham K. R. , Baeriswyl M. , Albrecht E. 
Published: September 2016

SummaryThe aim of this meta‐analysis was to assess the postoperative analgesic efficacy of sciatic nerve block when combined with femoral nerve block after total knee arthroplasty. Outcomes included resting pain scores (analogue scale, 0–100), intravenous morphine consumption at 12 h, 24 h and 48 h postoperatively, and functional outcomes comprising knee flexion, distance walked, and length of stay. Twelve randomised controlled trials were included, with a total of 600 patients. When combined with femoral nerve block, sciatic nerve block significantly reduced resting pain scores at 12 h postoperatively with a mean difference of 10 (95% CI: −15 to −5; p < 0.00001). Resting pain scores at 24 h, and intravenous morphine consumption at 12 h, 24 h and 48 h postoperatively were also significantly reduced, but without clinical significance beyond 12 h and without affecting functional outcomes. In conclusion, sciatic nerve block confers additional postoperative analgesia within the first 12 postoperative hours compared with femoral nerve block alone for patients undergoing total knee arthroplasty.
The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block: a dose‐finding randomised, controlled, double‐blind study
Authors: Abdulatif M. , Fawzy M. , Nassar H. , Hasanin A. , Ollaek M. , Mohamed H. 
Published: September 2016

SummaryThis randomised, controlled, double‐blind study investigated the effects of different doses of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block in patients undergoing arthroscopic knee surgery. Ultrasound‐guided femoral nerve block was performed before general anaesthesia using 25 ml of bupivacaine 0.5% combined with normal saline in the control group, and 25 μg, 50 μg or 75 μg of dexmedetomidine in three treatment groups (n = 15 for each group). All patients received a standard general anaesthetic and multimodal postoperative analgesic regimen. The use of the 50 μg and 75 μg dose levels of dexmedetomidine was associated with reduction of the onset time, extension of the duration of block, prolonged time to the first postoperative request for rescue analgesia, and reduced postoperative morphine requirements. The times to first request for postoperative analgesia were mean (SD) 10.8 (1.6) h in the control group and 11.0 (7.1), 21.8 (3.0) and 28.6 (10.0) in the 25 μg, 50 μg and 75 μg treatment groups, respectively. These times were significantly longer in the 50 μg and 75 μg treatment groups compared with the 25 μg (p < 0.0001) and control group (p < 0.0001). The total 24‐h postoperative morphine consumption was 7.6 (5.1) mg in the control group, and 6.5 (3.5), 3.9 (3.4), 1.8 (2.6) in the 25 μg, 50 μg and 75 μg treatment groups, respectively. Postoperative morphine consumption was significantly higher in the control group compared with the 50 μg (p = 0.045) and the 75 μg (p = 0.001) treatment groups. The best analgesic profile was achieved at the 75 μg dose, but this was associated with increased risk of hypotension.
Receptor‐interacting Protein 140 represses Sirtuin 3 to facilitate hypertrophy, mitochondrial dysfunction and energy metabolic dysfunction in cardiomyocytes
Authors: You J. , Yue Z. , Chen S. , Chen Y. , Lu X. , Zhang X. , Shen P. , Li J. , Han Q. , Li Z. , Liu P. 
Published: September 2016

AbstractAimThe transcriptional cofactor receptor‐interacting protein 140 (RIP140) is known as a deleterious regulator of cardiac mitochondrial function and energy metabolic homeostasis. This study revealed that RIP140 repressed Sirtuin 3 (SIRT3), a mitochondrial deacetylase that plays an important role in regulating cardiac function.MethodsRIP140 was overexpressed by adenovirus infection or was knocked down by RNA interference in neonatal rat cardiomyocytes.ResultsRIP140 overexpression repressed, while RIP140 silencing elevated the expression and activity of SIRT3. Ad‐RIP140 enhanced the expressions of the cardiac hypertrophic markers and increased cardiomyocyte surface area, whereas SIRT3 overexpression prevented the effect of Ad‐RIP140. Additionally, SIRT3 overexpression reversed Ad‐RIP140‐induced mitochondrial dysfunction and energy metabolic dysfunction, such as increase in oxidative stress, decrease in mitochondrial membrane potential and ATP production, as well as downregulation of mitochondrial DNA‐encoded genes and genes related to mitochondrial genome replication and transcription, mitochondrial oxidative phosphorylation and fatty acid oxidation. In contrast, SIRT3 silencing exacerbated RIP140‐induced cardiomyocyte hypertrophy and mitochondrial dysfunction. Furthermore, the repression of SIRT3 by RIP140 was dependent on estrogen‐related receptor‐α (ERRα). The involvement of peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) was ruled out of SIRT3 suppression by RIP140. RIP140 and PGC‐1α might act as functional antagonists on the regulation of SIRT3.ConclusionThis study indicates that suppression of SIRT3 by RIP140 facilitates the development of cardiomyocyte hypertrophy, mitochondrial dysfunction and energy metabolic dysfunction. Strategies targeting inhibition of RIP140 and upregulation of SIRT3 might improve cardiac energy metabolism and suggest therapeutic potential for heart diseases.
Translating QT interval prolongation from conscious dogs to humans
Authors: Dubois Vincent F. S. , Smania Giovanni , Yu Huixin , Graf Ramona , Chain Anne S. Y. , Danhof Meindert , Della Pasqua Oscar ,   on behalf of the Cardiovascular Safety Project Team,   TI Pharma PKPD Platform
Published: September 2016

AimIn spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic–pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug‐specific parameters describing QT interval prolongation in dogs and in humans.MethodsUsing estimates of the drug‐specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT‐prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between −0.98 ms μM–1 and 6.1 ms μM–1 in dogs and −10 ms μM–1 and 90 ms μM–1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species.ResultsFor compounds without a mixed ion channel block, a correlation was observed between the drug‐specific parameter in dogs and humans (y = −1.709 + 11.6x; R2 = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6‐fold larger than in dogs.ConclusionsTogether with information about the expected therapeutic exposure, the evidence of a correlation between the compound‐specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans.
The impact of serious adverse drug reactions: a population‐based study of a decade of hospital admissions in New South Wales, Australia
Authors: Walter Scott R. , Day Richard O. , Gallego Blanca , Westbrook Johanna I. 
Published: September 2016

AimsAdverse drug reactions (ADRs) have major impacts on patients and the hospital system. Methods identifying ADRs from selected International Classification of Diseases–10th revision (ICD‐10) diagnosis and external cause codes can be applied to population‐level hospital admissions data, enabling the study of rare, yet serious ADRs. The present study aimed to use ICD10‐based methods to identify four types of serious idiosyncratic ADRs in Australia, and to assess changes in incidence and their impact on length of stay (LOS), readmission and in‐hospital mortality.MethodsThe study used a census of hospital admission data from New South Wales between July 2000 and June 2012. Changes in incidence rates over time relative to a control group were estimated using log‐linear regression. To assess impacts on LOS, readmission and mortality, each ADR case was matched with five controls, and cases were compared with controls via generalized linear models appropriate to each outcome.ResultsThe incidence of three ADR types showed a significant increase over time relative to controls, while the fourth type showed no evidence of change. All ADR types were significantly associated with an increase in LOS of between 22% and 328%. Significant increases in risk of readmission or death were only observed for some ADR types.ConclusionsReducing the incidence of idiosyncratic ADRs is challenging. ICD10‐based methods support population‐level analyses that can provide important insights into the effects and changes in ADRs over time. This, combined with strategies related to both patient care and drug monitoring pre‐ and post‐commercial release, provides ways forward.
Increased chemotaxis and activity of circulatory myeloid progenitor cells may contribute to enhanced osteoclastogenesis and bone loss in the C57BL/6 mouse model of collagen-induced arthritis
Authors: Ikić Matijašević M , Flegar D , Kovačić N , Katavić V , Kelava T , Šućur A , Ivčević S , Cvija H , Lazić Mosler E , Kalajzić I , Marušić A , Grčević D 
Published: September 2016

Summary
Our study aimed to determine the functional activity of different osteoclast progenitor (OCP) subpopulations and signals important for their migration to bone lesions, causing local and systemic bone resorption during the course of collagen-induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II collagen (CII), and assessed by clinical scoring and detection of anti-CII antibodies. We observed decreased trabecular bone volume of axial and appendicular skeleton by histomorphometry and micro-computed tomography as well as decreased bone formation and increased bone resorption rate in arthritic mice in vivo. In the affected joints, bone loss was accompanied with severe osteitis and bone marrow hypercellularity, coinciding with the areas of active osteoclasts and bone erosions. Flow cytometry analysis showed increased frequency of putative OCP cells (CD3–B220–NK1.1–CD11b–/loCD117+CD115+ for bone marrow and CD3–B220–NK1.1–CD11b+CD115+Gr-1+ for peripheral haematopoietic tissues), which exhibited enhanced differentiation potential in vitro. Moreover, the total CD11b+ population was expanded in arthritic mice as well as CD11b+F4/80+ macrophage, CD11b+NK1.1+ natural killer cell and CD11b+CD11c+ myeloid dendritic cell populations in both bone marrow and peripheral blood. In addition, arthritic mice had increased expression of tumour necrosis factor-α, interleukin-6, CC chemokine ligand-2 (Ccl2) and Ccl5, with increased migration and differentiation of circulatory OCPs in response to CCL2 and, particularly, CCL5 signals. Our study characterized the frequency and functional properties of OCPs under inflammatory conditions associated with arthritis, which may help to clarify crucial molecular signals provided by immune cells to mediate systemically enhanced osteoresorption.
Role of proneurotensin as marker of paediatric coeliac disease
Authors: Montén C , Torinsson Naluai Å , Agardh D 
Published: September 2016

Summary
Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear factor kappa B (NF-κB) and interleukin (IL)−8 secretion or anti-inflammatory through epidermal growth factor receptors. NT mRNA is down-regulated in duodenal biopsies of children with untreated coeliac disease. The aim of this study was to investigate if plasma pro-NT levels correlated with the degree of intestinal mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children with coeliac disease. Fasting plasma samples from 96 children with coeliac disease and 89 non-coeliac disease controls were analysed for NT precursor fragment pro-NT 1–117 by a chemiluminometric immunoassay. Pro-NT levels were compared with NT mRNA from duodenal biopsies, assessed previously with quantitative polymerase chain reaction (PCR). Illumina core exome arrays were used for human leucocyte antigen (HLA) typing and the Marsh criteria applied to score mucosal damage. Tissue TGA was measured by radio binding assay. A general linear model compared pro-NT levels with diagnosis of coeliac disease, Marsh score and HLA DQ haplotype. Spearman's rank test was used to compare pro-NT levels with tTGA, age and duodenal NT mRNA levels, respectively. Plasma pro-NT levels were elevated in children with coeliac disease (median 23 pmol/l higher, P = 0·003) and in those with severe intestinal mucosal damage (median 24 pmol/l higher for ≥ Marsh 3b versus not, P = 0·0004). Pro-NT levels correlated further with tTGA (r2 = 0·22, P = 0·002), but not with duodenal NTS mRNA levels (r2 = −0·12, P = 0·14). Pro-NT was not associated with any of the HLA risk-haplotypes. Elevated peripheral pro-NT levels reflect more severe forms of active coeliac disease, indicating a potential role of NT in intestinal inflammation.
Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome
Authors: Apostolou E , Kapsogeorgou E K , Konsta O D , Giotakis I , Saridaki M I , Andreakos E , Tzioufas A G 
Published: September 2016

SummaryType III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)−28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls. All type III IFN family members were detected in ductal and acinar epithelia of MSGs from both SS patients and sicca controls. IFN-λ2/IL-28A and IFN-λ3/IL-28B were also expressed in infiltrating mononuclear cells. In SS patients with intermediate MSG lesions, the epithelial expression of IFN-λ2/IL-28A was more intense compared to sicca controls (P &lt; 0·05). The receptor IFN-λR1/IL-28Ra was detected in all types of cells except fibroblasts, and was exceptionally strong in plasmatocytoid dendritic cells, indicating that they are susceptible to type III IFN-mediated regulation. In the periphery, only IFN-λ1/IL-29 was detected in the sera and was elevated significantly in SS patients with intermediate MSG inflammatory lesions compared to sicca controls (P = 0·0053). None of the type III IFNs was expressed constitutively in resting SGECs; they were all induced readily by TLR-3 stimulation, suggesting that the in-situ epithelial expression can be attributed to local microenvironment. Type III IFNs are expressed in MSGs in a similar pattern to type I IFNs and their expression is probably subjected to micro-environmental regulation, suggesting that they are implicated in the inflammatory processes occurring in the affected exocrine glands.
Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies
Authors: Borte M , Kriván G , Derfalvi B , Maródi L , Harrer T , Jolles S , Bourgeois C , Engl W , Leibl H , McCoy B , Gelmont D , Yel L 
Published: September 2016

Summary
A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2–67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient-year, P &lt; 0·0001); the rate of all infections was 4·38/patient-year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3-4·1) h using mainly one to two administration sites [median = 2 sites (range = 1–5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.
Values of radiological examinations for the diagnosis and prognosis of invasive bronchial‐pulmonary aspergillosis in critically ill patients with chronic obstructive pulmonary diseases
Authors: Huang Linna , He Hangyong , Ding Yi , Jin Jingjing , Zhan Qingyuan 
Published: September 2016

AbstractIntroductionThe important role of radiological examinations of invasive pulmonary aspergillosis (IPA) in patients with neutropenia has been well studied; however, little is known about IPA in critically ill chronic obstructive pulmonary disease (COPD) patients.ObjectivesTo evaluate the value of radiological examinations in the diagnosis and prognosis of invasive bronchial‐pulmonary aspergillosis (IBPA) in critically ill COPD patients.MethodsWe included 61 critically ill COPD patients in the intensive care unit (ICU) in a retrospective, single‐center cohort study.ResultsAll of the patients were classified as IBPA group (n = 21) or non‐IBPA group (n = 40). The chest computed tomography (CT) image analysis showed that the IBPA group had the highest percent of patchiness (76.2%), followed by multiple nodules (33.3%), angio‐invasive patterns (including halo sign, wedge consolidation and air‐crescent sign/cavity with a relatively low percent of 19%, 19% and 28.5%, respectively), and the multiple nodules that were distributed along the airway provided the most specific image, with the highest specificity of 92.5%. Compared to the survivors in the IBPA group, non‐surviving patients had a higher percent of large consolidation (0% vs. 45.5%,P = .035). When the new effusions appeared on a chest x‐ray (CXR), the creatinine (140.4 μmol/L vs. 64.0 μmol/L,P = .010) and PaO2/FiO2(188 mm Hg vs. 222 mm Hg,P = .034) rate deteriorated.ConclusionsMultiple nodules that were distributed along with broncho‐vascular bundles were relatively common and specific in critically ill COPD patients with IBPA. Deteriorated CXR combined with specific laboratory examinations, even when appropriate antibiotics were used, could indicate a diagnosis of IBPA. Large consolidations might be considered as poor prognostic indicators.
Isolated diffusing capacity reduction is a common clinical presentation in deployed Iraq and Afghanistan veterans with deployment‐related environmental exposures
Authors: Falvo Michael J. , Helmer Drew A. , Klein Jacquelyn C. , Osinubi Omowunmi Y. , Ndirangu Duncan , Patrick‐DeLuca Lydia A. , Sotolongo Anays M. 
Published: September 2016

AbstractFollowing deployment to Iraq and Afghanistan (“post‐9/11”), a spectrum of respiratory conditions has been reported; however, there are few published reports of objective physiologic data or later experience of symptoms and function. To better understand the post‐deployment clinical presentation, we conducted a retrospective review of pulmonary function testing in 143 veterans referred to our tertiary care clinic for post‐deployment health concerns. More than 75% of our sample had normal lung volumes and spirometry on pulmonary function testing; however, an isolated reduction in lung diffusing capacity (DLCO) was observed in 30% of our sample of post‐9/11 veterans. An isolated reduction in DLCO is a rare pattern in primary‐care seeking dyspneic patients, but is commonly associated with underlying pulmonary disease. Post‐9/11 veterans with respiratory complaints and an isolated reduction in DLCO should undergo further evaluation.
A case report of acute fibrinous and organizing pneumonia with pneumothorax and avian exposure history
Authors: Chiu Kam Yu , Li Jian Guo , Gu Ying Ying 
Published: September 2016

AbstractAcute fibrinous and organizing pneumonia (AFOP) is an uncommon variant of acute lung injury. Here, we report a patient with AFOP and a previously unreported condition, pneumothorax. After our experience with this case, we suggest that exposure to birds may be associated with AFOP; pneumothorax can develop in patients with AFOP; and glucocorticoids are very effective for treating AFOP.
Sola Scriptura: Strengths and Challenges
Authors: Jacobson Diane 
Published: September 2016

AbstractWhen Luther's notion of sola Scriptura is nuanced and properly understood, it is engaging and true in its assertions. However, in today's world, the use of the expression sola Scriptura may be more problematic than helpful. This point is argued for three reasons: Lutheran relationships with Catholics; the rise of American fundamentalism; and the parallel rise of “nones,” that largely young group of agnostics (sometimes atheists) not affiliated with any organized religion. By considering these issues, we can see how the notion still has relevance for theology and for the broader church, and how this notion helps us to preach, teach, and live the gospel in this time and place.