bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality and prognostic factors of patients who have blood cultures performed in the emergency department: a cohort study
Authors: Lindvig Katrine P. , Nielsen Stig L. , Henriksen Daniel P. , Jensen Thøger G. , Kolmos Hans Jørn , Pedersen Court , Vinholt Pernille J. , Lassen Annmarie T.
Published: February 2015

Background

Early identification and treatment of patients with severe infection improve their prognosis. The aims of this study were to describe the 30-day mortality and to identify prognostic factors among blood-cultured patients in a medical emergency department (MED).

Patients and methods

This was a hospital-based cohort study including all adult (≥15 years old) blood-cultured patients at the MED at Odense University Hospital between 1 August 2009 and 31 August 2011.

Results

During the study period, 5499/11 988 (45.9%) patients had blood cultures performed within 72 h of arrival and were included in the study. Of those included, 2631 (47.8%) were men, median age 69 years (range 15–103), and 418 (7.6%) were diagnosed with bacteraemia. The overall 30-day mortality among blood-cultured patients was 11.0% (10.2–11.9). In a multivariate Cox regression model, age of more than 80 years [hazard ratio (HR) 4.6 (95% CI 3.6–6.0)], at least two organ failure [HR 3.6 (2.9–4.5)], bacteraemia [HR 1.4 (1.1–1.8)], Charlson Comorbidity Index of at least 2 h [HR 1.7 (1.3–2.0)], SIRS [HR 1.5 (1.2–1.7)], a history of alcohol dependency [HR 1.7 (1.3–2.3)] and late drawing of blood cultures 24–48 h after arrival [HR 1.7 (1.3–2.2)] were found to be prognostic factors of mortality among blood-cultured patients in the MED.

Conclusion

Among blood-cultured patients in the MED, we found an 11.0% overall 30-day mortality. Factors associated with 30-day mortality were age more than 80 years, at least two organ failure, bacteraemia, Charlson Comorbidity Index of at least 2, SIRS, a history of alcohol dependency and late drawing of blood cultures.
Controversial Effects of Exogenous Testosterone on Cardiovascular Diseases
Authors: Al-Khazaali Ali , Arora Rohit , Muttar Saad
Published: February 2015

The use of testosterone (T) among men aged 40 years or older was increased more than 3 times from 0.81% in 2001 to 2.91% in 2011. Until recently, the majority of the studies did not show any increased cardiovascular (CV) risk by using T in male patients with hypogonadism. What is more, some studies had observed a protective effect of using T against CV diseases. However, in 2010, a randomized clinical trial (RCT) was intended to study the advantage of T gel in older men with limitations in mobility; the study was stopped due to unexpected high prevalence of CV adverse outcome. These findings were confirmed by 2 other studies published in November of 2013 and January of 2014. Consequently, the Food and Drug Administration (FDA) had announced in January 2014 that it will reassess the safety of those treatments. Meanwhile, the agency had not reached to a definitive conclusion that FDA-approved testosterone therapy raises the risk of stroke, heart attack, or death. A report released in the broadcast of the NBC Nightly News in September of this year that the FDA says “there's little evidence that T boosting drugs taken by millions of American men are actually effective.” NBC notes that the agency also pointed out that it was not convinced that they carry serious risk either. “The condition has been marketed as low ‘T’, and the medications are offered to help with low sex drive and fatigue among some men,” notes NBC. The European Medicines Agency EMA's Pharmacovigilance Risk Assessment Committee has also responded to the concern of potential CV adverse outcomes associated with the use of T, and they have concluded in their October meeting of this year that the use of T in men who do not produce enough T raises the risk of heart diseases. In our review, we highlighted the association between exogenous T and major adverse CV outcomes. Additionally, we focused on the interplay between exogenous T and some endocrine abnormalities such as diabetes mellitus type 2, metabolic syndrome, dyslipidemia, and obesity.
Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers
Authors: Shah Yasar , Iqbal Zafar , Ahmad Lateef , Khuda Fazli , Khan Abad , Khan Abbas , Khan Muhammad Imran , Ismail
Published: February 2015

The current study aimed at the evaluation of, in vivo, the effect of omeprazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Omeprazole is an acid suppressant and CYP2C9, CYP3A4, and CYP2C19 substrate and inhibitor, as well as inhibitor of transporters (like P-gp). This was a randomized, open-label, 2-period, crossover study. Healthy male volunteers (N = 20), divided into 2 groups, were given single oral doses of rosuvastatin 40 mg either alone (treatment period I) or concomitantly with omeprazole 40-mg capsule (treatment period II). Plasma concentrations of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) were quantified by a validated liquid chromatography–tandem mass spectrometry method developed in our laboratory. An insignificant decrease (P > 0.05) has been observed in the values of maximum plasma concentrations, clearance, and half-life of rosuva, whereas an insignificant increase (P > 0.05) has been observed in the area under the plasma concentration–time curves from zero time to the last measurable concentration

JOURNAL/ajthe/04.03/00045391-201611000-00034/inline-formula1/v/2023-09-17T022504Z/r/image-tiff

, that extrapolated to infinity

JOURNAL/ajthe/04.03/00045391-201611000-00034/inline-formula2/v/2023-09-17T022504Z/r/image-tiff

, and mean residence time values after concomitant administration with omeprazole. Although omeprazole concomitant administration altered the pharmacokinetics of NDM-rosuva metabolite significantly, rosuva's very little metabolism (10%) suggests that these changes are of no clinical significance. Concomitant administration of omeprazole with rosuva did not alter the pharmacokinetics of rosuva in healthy volunteers. These data are consistent with other reported studies, indicating that rosuva is not a good candidate for metabolism-based drug–drug interactions. Therefore, rosuva can be administered safely along with omeprazole.
Selection constrains phenotypic evolution in a functionally important plant trait
Authors: Muir Christopher D.
Published: February 2015

A long-standing idea is that the macroevolutionary adaptive landscape – a ‘map’ of phenotype to fitness – constrains evolution because certain phenotypes are fit, while others are universally unfit. Such constraints should be evident in traits that, across many species, cluster around particular modal values, with few intermediates between modes. Here, I compile a new global database of 599 species from 94 plant families showing that stomatal ratio, an important functional trait affecting photosynthesis, is multimodal, hinting at distinct peaks in the adaptive landscape. The dataset confirms that most plants have all their stomata on the lower leaf surface (hypostomy), but shows for the first time that species with roughly half their stomata on each leaf surface (amphistomy) form a distinct mode in the trait distribution. Based on a new evolutionary process model, this multimodal pattern is unlikely without constraint. Further, multimodality has evolved repeatedly across disparate families, evincing long-term constraint on the adaptive landscape. A simple cost-benefit model of stomatal ratio demonstrates that selection alone is sufficient to generate an adaptive landscape with multiple peaks. Finally, phylogenetic comparative methods indicate that life history evolution drives shifts between peaks. This implies that the adaptive benefit conferred by amphistomy – increased photosynthesis – is most important in plants with fast life histories, challenging existing ideas that amphistomy is an adaptation to thick leaves and open habitats. I conclude that peaks in the adaptive landscape have been constrained by selection over much of land plant evolution, leading to predictable, repeatable patterns of evolution.
A minimalistic resource allocation model to explain ubiquitous increase in protein expression with growth rate
Authors: Barenholz Uri , Keren Leeat , Segal Eran , Milo Ron
Published: February 2015

Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate.

We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganismE.colias reflected in two recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes could be part of a global effect, not requiring specific cellular control mechanisms.
Arabidopsis Glutamate Receptor Homolog3.5 Modulates Cytosolic Ca2+ Level to Counteract Effect of Abscisic Acid in Seed Germination
Authors: Kong Dongdong , Ju Chuanli , Parihar Aisha , Kim So , Cho Daeshik , Kwak June M.
Published: February 2015

Seed germination is a critical step in a plant’s life cycle that allows successful propagation and is therefore strictly controlled by endogenous and environmental signals. However, the molecular mechanisms underlying germination control remain elusive. Here, we report that the Arabidopsis (Arabidopsis thaliana) glutamate receptor homolog3.5 (AtGLR3.5) is predominantly expressed in germinating seeds and increases cytosolic Ca2+ concentration that counteracts the effect of abscisic acid (ABA) to promote germination. Repression of AtGLR3.5 impairs cytosolic Ca2+ concentration elevation, significantly delays germination, and enhances ABA sensitivity in seeds, whereas overexpression of AtGLR3.5 results in earlier germination and reduced seed sensitivity to ABA. Furthermore, we show that Ca2+ suppresses the expression of ABSCISIC ACID INSENSITIVE4 (ABI4), a key transcription factor involved in ABA response in seeds, and that ABI4 plays a fundamental role in modulation of Ca2+-dependent germination. Taken together, our results provide molecular genetic evidence that AtGLR3.5-mediated Ca2+ influx stimulates seed germination by antagonizing the inhibitory effects of ABA through suppression of ABI4. These findings establish, to our knowledge, a new and pivotal role of the plant glutamate receptor homolog and Ca2+ signaling in germination control and uncover the orchestrated modulation of the AtGLR3.5-mediated Ca2+ signal and ABA signaling via ABI4 to fine-tune the crucial developmental process, germination, in Arabidopsis.
The Role of the Plant-Specific ALTERED XYLOGLUCAN9 Protein in Arabidopsis Cell Wall PolysaccharideO-Acetylation
Authors: Schultink Alex , Naylor Dan , Dama Murali , Pauly Markus
Published: February 2015

A mutation in the ALTERED XYLOGLUCAN9 (AXY9) gene was found to be causative for the decreased xyloglucan acetylation phenotype of the axy9.1 mutant, which was identified in a forward genetic screen for Arabidopsis (Arabidopsis thaliana) mutants. The axy9.1 mutant also exhibits decreased O-acetylation of xylan, implying that the AXY9 protein has a broad role in polysaccharide acetylation. An axy9 insertional mutant exhibits severe growth defects and collapsed xylem, demonstrating the importance of wall polysaccharide O-acetylation for normal plant growth and development. Localization and topological experiments indicate that the active site of the AXY9 protein resides within the Golgi lumen. The AXY9 protein appears to be a component of the plant cell wall polysaccharide acetylation pathway, which also includes the REDUCED WALL ACETYLATION and TRICHOME BIREFRINGENCE-LIKE proteins. The AXY9 protein is distinct from the TRICHOME BIREFRINGENCE-LIKE proteins, reported to be polysaccharide acetyltransferases, but does share homology with them and other acetyltransferases, suggesting that the AXY9 protein may act to produce an acetylated intermediate that is part of the O-acetylation pathway.
Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C‐terminal domain and laminin gamma‐1
Authors: Ishida Syuichi , Takahashi Kazuo , Kanaoka Miwa , Okawa Tomoko , Tateishi Chiharu , Yasukochi Atsushi , Ishii Norito , Li Xiaoguang , Hashimoto Takashi , Aihara Michiko
Published: February 2015

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180‐kDa bullous pemphigoid antigen (BP180) non‐collagenous 16a (NC16a) domain or anti‐laminin‐γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C‐terminal domain and laminin‐γ1. A 64‐year‐old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl‐split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C‐terminal domain and 200‐kDa laminin‐γ1 in normal human dermal extract.
The Effects of Racemization Rate for Age Estimation of Pink Teeth
Authors: Sakuma Ayaka , Saitoh Hisako , Ishii Namiko , Iwase Hirotaro
Published: February 2015

Pink teeth is thought to result from the seepage of hemoglobin caused by dental pulp decomposition. We investigated whether racemization can be applied for age estimation in cases of pink teeth where the whole tooth is used. The pink teeth used were three cases and the normal teeth for control were five mandibular canines of known age. Age of the pink teeth was calculated on the basis of regression formula obtained from the five control teeth. Only a slight error was noted between the actual and estimated ages of the pink teeth (R2 = 0.980, r = 0.990): Cases 1–3 actually aged 23, 53, and 59 years were estimated to be 26, 52, and 60 years. Based on our results of testing pink teeth of known age, we suggest that racemization techniques allow for the age estimation of pink teeth using the same methods for normally colored teeth.
Advantage of ForensiX Swabs in Retrieving and Preserving Biological Fluids
Authors: Mawlood Shakhawan K. , Alrowaithi Majid , Watson Nigel
Published: February 2015

This study compares two novel swabs (forensiX) with a standard cotton swab (EUROTUBE) for the collection of saliva stains on glass slide for STR analysis. ForensiX collection tubes are a standard cotton swab in an “active drying” tube, where swab sample is soon dried by its innovative tube surface of the wall. The other is forensiX Nylon Flocked Swab. The study is two phases: The first “phase” assesses swab types regarding to retrieve ability of saliva. The second “phase” compares the drying ability of each swab to assess how crime samples would fare when left in storage. The main result showed that “active drying” is effective to store swabbed sample. The forensiX swabs generally are effective for higher (twofold to fourfold) DNA yield compared to delta lab swab (around 750 pg and 250 pg from 0.5 μL of saliva), respectively. These findings demonstrate the importance of drying performance in the preservation of DNA and swab selection.
PE‐Swab Direct STR Amplification of Forensic Touch DNA Samples
Authors: Liu Jason Y.
Published: February 2015

The PE‐Swab direct STR amplification workflow was developed to process low‐level “touch DNA” samples. In this workflow, a forensic sample is first collected on a 4‐mm PE‐Swab (a novel sample collection device); two 2‐mm punches containing collected samples are then generated from the PE‐Swab and directly amplified for STR typing. Compared to the conventional STR workflow, which involves DNA extraction, purification, and elution volume reduction, the PE‐Swab direct STR amplification workflow does not require sample preparation and takes <60 sec before a touch sample is ready for STR amplification. Because there is no DNA loss due to sample preparation, the PE‐Swab workflow is more sensitive than the conventional STR workflow. The average peak height per sample obtained by the PE‐swab workflow is 3 times higher than that from the conventional workflow with both low‐level single source and two‐contributor mixture samples tested in this study.
Sex differences in risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms in China
Authors: He Qun , Yang Yong , Xia Ming , Li Gui‐Zhong , Zhang Ning , Wu Shi‐Liang , Jin Rui , Shen Hong
Published: February 2015

Aim

The aim of the present study was to identify sex differences of risk factors for interstitial cystitis (IC)/painful bladder syndrome (PBS) in patients with lower urinary tract symptoms (LUTS) without urinary tract infection or benign prostate hyperplasia in China.

Patients and Methods

A total of 954 outpatients with LUTS presenting for care to urology clinics in many hospitals on a national scale were surveyed using a standardized questionnaire. The definitions for PBS, based on the O'Leary–Sant IC symptom and problem indices, was used. The prevalence of possible risk factors was analysed using the Fisher's exact test, Pearson's χ2‐test and binary logistic regression methods.

Results

Of the multicentre patients surveyed (491 women and 463 men), 44.7 per cent (427/954) met the criteria for PBS. There was a significant difference between women and men [51.7 per cent (254/491) vs 37.3 per cent (173/463), P > 0.05]. After adjusting for confounding factors, bladder pain was found to be significantly associated with the consumption of stimulatory foods [odds ratio (OR): 3.85, 95 per cent confidence interval (CI): 1.58–9.36, P = 0.003] and anorectal disease (OR: 2.76, 95 per cent CI: 1.09–7.04, P = 0.03) in women. Caffeine beverage intake (OR: 3.54, 95 per cent CI: 1.54–8.12, P = 0.003) was identified the only modifiable association noted in a multivariate analysis of men. Factors in men significantly associated with an increased risk of IC/PBS were the consumption of caffeinated beverages (OR: 1.43, 95 per cent CI: 1.16–1.75, P = 0.001) and holding in urine (OR: 1.18, 95 per cent CI: 1.03–1.36, P = 0.034).

Conclusions

A higher incidence of IC was founded in LUTS outpatients without urinary tract infection or benign prostate hyperplasia in China. Stimulating foods, irritable bowel, gynaecologically‐infected diseases and anorectal disease are potential risk factors for IC/PBS in women. Caffeinated beverages and holding in urine are potential risk factors for IC/PBS in men.
Fat grafting: A safe and effective treatment of craniofacial depression
Authors: Li George K.H. , Chung Joseph H.P. , Liu Lawrence H.L. , Chow Velda L.Y. , Lau Gregory Ian S.K. , Chan Richie C.L.
Published: February 2015

Aim

Many techniques have been described to correct craniofacial depression defect to achieve satisfactory result but they involve complicated reconstruction and considerable donor site morbidities. The result of fat grafting in correction of the defects is demonstrated in this study.

Methods

Six patients were treated during the period of November 2005 to August 2009. Median age was 47 years old. Diagnosis included post craniectomy forehead depression, lupus folliculitis, lymphoma panniculitis and Parry Romberg disease. Fat graft was harvested from abdomen, processed and then injected percutaneously to correct the defects. Total 13 procedures were performed, 9 under local anaesthesia, 3 under general anaesthesia and 1 under intravenous sedation. Standard facial photographs were taken before and at 4 months after the last treatment for comparison. The patients and 2 independent surgeons then score their level of satisfaction by using a score system from 0 to 10.

Results

The median hospital stay and operation time are 1 day and 67.5 minutes respectively. The treatment session ranges from 1 to 6 with median of 1 session. Median volume of fat graft injected is 15.5cc. The patients and the two plastic surgeons rank moderate to high level of satisfaction. The median satisfaction scores are 8.0, 8.5 and 8.5 out of 10 in these groups accordingly. Injection site haematoma and transient facial nerve palsy happened in one patient each. The morbidities resolved spontaneously.

Conclusion

Fat grafting is demonstrated to be safe and effective to correct craniofacial depression with high level of satisfaction and minimal morbidities.
A novel Wolbachia strain from the rice moth Corcyra cephalonica induces reproductive incompatibility in the whitefly Bemisia tabaci: sequence typing combined with phenotypic evidence
Authors: Hu Hong‐Yan , Li Zheng‐Xi
Published: February 2015

Wolbachia are a group of maternally inherited bacteria frequently found in arthropods and filarial nematodes. They have recently attracted attention for their ecological roles in manipulating host reproduction, their potential use in biological control of pest insects and medical significance. Classification of Wolbachia strains is currently solely based on molecular methods. However, the strains even with identical sequence types may induce different host phenotypes. Here we isolated a Wolbachia strain from the rice moth Corcyra cephalonica (designated as wCcep_B_BJ), which was shown to share multilocus sequence typing and Wolbachia surface protein hypervariable region profiles with a cytoplasmic incompatibility (CI)‐inducing strain in supergroup B, but the phenotype wCcep_B_BJ may induce needs to be determined. We thus transinfected it into the whitefly Bemisia tabaci harbouring an A‐Wolbachia through nymphal microinjection. Fluorescent in situ hybridization demonstrated that wCcep_B_BJ was successfully transinfected into B. tabaci and transmitted to offspring through host eggs. Reciprocal cross showed that wCcep_B_BJ induced a strong bidirectional CI in the transinfected host without imposing a significant cost on female fecundity. Our results suggest that wCcep_B_BJ may be a promising strain for biocontrol of B. tabaci, an important agricultural pest insect.
Clinical features of lung adenocarcinomas with epidermal growth factor receptor mutations and miliary disseminated carcinomatosis
Authors: Kim Hee Joung , Kang Seong Hui , Chung Hyun Woo , Lee Jong Sik , Kim Sun Jong , Yoo Kwang Ha , Lee Kye Young
Published: February 2015

Background

We have occasionally encountered advanced lung cancer patients with disseminated carcinomatosis throughout the body and/or within the lung. This study investigated the clinical characteristics and outcomes of advanced lung adenocarcinoma patients with miliary disseminated carcinomatosis.

Methods

Patients with adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations who presented with miliary disseminated carcinomatosis (either intrapulmonary or distant site) were enrolled in the study. Clinical characteristics, treatment responses, and survival outcomes were collected from medical records.

Results

The most frequent EGFR mutation was an in‐frame deletion in exon 19 (n = 44, 68.8%). Arginine substitution of leucine 858 in exon 21 and alanine substitution of glycine 719 in exon 18 were detected in 19 patients (29.7%) and one patient (1.6%), respectively. Patients with miliary disseminated carcinomatosis tended to be female and non‐smokers. They expressed the E19 deletion more frequently than patients without miliary dissemination and had shorter progression‐free survival times in response to EGFR tyrosine kinase inhibitors (9.7 vs. 12.8 months, P = 0.003) and poorer overall survival (15.9 vs. 29.0 months, P = 0.077). Multivariate analyses revealed that metabolic tumor volume correlated with shorter overall survival time.

Conclusions

Our data indicate that lung adenocarcinoma patients with miliary dissemination have relatively shorter survival times than those without miliary dissemination. The poor prognosis of patients with miliary dissemination may reflect a high tumor burden, as represented by metabolic tumor volume.
What is the Relationship Between Audit Partner Busyness and Audit Quality?
Authors: Goodwin John , Wu Donghui
Published: February 2015

Contemporaneous studies generally find a negative relationship between audit partner busyness (APB), measured as the number of clients in an audit partner's portfolio, and audit quality. Their argument is that a busy partner does not devote sufficient time to properly audit his average client. Contrary to these studies, we argue that when busyness is optimally chosen by the partner, in equilibrium, there is no causal relationship between APB and audit quality. Using Australian data for the 1999–2010 period, we show that APB is not reliably linked to audit quality, consistent with this equilibrium theory. We argue that causality can be ascribed to the APB‐audit quality relationship when accounting scandals exogenously shocked the Australian audit market during the 2002–04 period and APB likely deviated from optimum levels. Supporting this disequilibrium view, we find that higher APB reduces a partner's propensity to issue first‐time going‐concern opinions during this period. Our evidence highlights the importance of the equilibrium condition in testing empirical associations between audit outcomes and endogenous auditor attributes, and shows that the detrimental effect of APB on audit quality is not as pervasive as contemporaneous studies suggest.
Epidural analgesia in patients with traumatic rib fractures: a systematic review of randomised controlled trials
Authors: DUCH P. , MØLLER M. H.
Published: February 2015

Background

Traumatic rib fractures are a common condition associated with considerable morbidity and mortality. Observational studies have suggested improved outcome in patients receiving continuous epidural analgesia (CEA). The aim of the present systematic review of randomised controlled trials (RCTs) was to assess the benefit and harm of CEA compared with other analgesic interventions in patients with traumatic rib fractures.

Methods

We performed a systematic review with meta‐analysis and trial sequential analysis (TSA). Eligible trials were RCTs comparing CEA with other analgesic interventions in patients with traumatic rib fractures. Cumulative relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were estimated, and risk of systematic and random errors was assessed. The predefined primary outcome measures were mortality, pneumonia and duration of mechanical ventilation.

Results

A total of six trials (n = 223) were included; all were judged as having a high risk of bias. In the conventional meta‐analyses, there was no statistically significant difference in mortality (RR 2.18, 95% CI 0.21–22.42; P = 0.51; I2 = 0%), duration of mechanical ventilation (MD −7.53, 95% CI −16.32 to 1.26; P = 0.09; I2 = 91%) or pneumonia (RR 0.49, 95% CI 0.19–1.25; P = 0.13; I2 = 0%) between CEA and other analgesic interventions. Subgroup analyses and sensitivity analyses, including TSA confirmed the results.

Conclusion

The quality and quantity of evidence for the use of CEA in patients with traumatic rib fractures is low, and there is no firm evidence for benefit or harm of CEA compared with other analgesic interventions. Well‐powered RCTs with low risk of bias reporting clinically relevant patient‐centred outcome measures are needed.
The evidence of neuraxial administration of analgesics for cancer‐related pain: a systematic review
Authors: Kurita G. P. , Benthien K. S. , Nordly M. , Mercadante S. , Klepstad P. , Sjøgren P. ,   the European Palliative Care Research Collaborative (EPCRC)
Published: February 2015

Background

The present systematic review analysed the existing evidence of analgesic efficacy and side effects of opioids without and with adjuvant analgesics delivered by neuraxial route (epidural and subarachnoid) in adult patients with cancer.

Methods

Search strategy was elaborated with words related to cancer, pain, neuraxial route, analgesic and side effects. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. Studies were analysed according to methods, results, quality of evidence, and strength of recommendation.

Results

The number of abstracts retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented clinical and methodological diversity that precluded a meta‐analysis. They also presented several limitations, which reduced study internal validity. However, they demonstrated better pain control for all interventions analysed. Side effects were described, but there were few significant differences in favour of the tested interventions.

Conclusion

Heterogeneous characteristics and several methodological limitations of the studies resulted in evidence of low quality and a weak recommendation for neuraxial administration of opioids with or without adjuvant analgesics in adult patients with cancer.
Central venous pressure: we need to bring clinical use into physiological context
Authors: SONDERGAARD S. , PARKIN G. , ANEMAN A.
Published: February 2015

Background

The place of central venous pressure (CVP) measurement in acute care has been questioned during the past decade. We reviewed its physiological importance, utility and clinical use among anaesthetists and intensivists.

Methods

A literature search using the PubMed, Cochrane, Scopus and Web of Science databases was performed in regard to details of the physiology, measurement and interpretation of CVP. A questionnaire was conducted among members of the European Society of Intensive Care Medicine concerning knowledge and uses of CVP.

Results

Aligning pressure transducers to the phlebostatic axis was handled inadequately. The unsuitability of CVP to assess the intravascular volume state was generally recognised by clinicians. Still, many used CVP to guide volume resuscitation in the absence of a cardiac output monitor, while the literature positioned CVP as a useful haemodynamic variable only in the expanded context of being one determinant of the driving pressure for venous return and hence cardiac output.

Conclusion

The correct measurement of CVP is pivotal to its proper clinical application. This relates to defining the pressure gradient for venous return and heart efficiency. The clinical appreciation of CVP should be restored by educational efforts of its physiological context.
Deep neuromuscular block reduces intra‐abdominal pressure requirements during laparoscopic cholecystectomy: a prospective observational study
Authors: VAN WIJK R. M. , WATTS R. W. , LEDOWSKI T. , TROCHSLER M. , MORAN J. L. , ARENAS G. W. N.
Published: February 2015

Background

Laparoscopic surgery causes specific post‐operative discomfort and intraoperative cardiovascular, pulmonary, and splanchnic changes. The CO2 pneumoperitoneum‐related intra‐abdominal pressure (IAP) remains one of the main drivers of these changes. We investigated the influence of deep neuromuscular blockade (NMB) on IAP and surgical conditions.

Methods

This is an open prospective single‐subject design study in 20 patients (14 female/6 male) undergoing laparoscopic cholecystectomy. Inclusion criteria were 18 years or older, and American Society of Anesthesiologists classification 1 to 3. Under a standardised anaesthesia, lowest IAP providing adequate surgical conditions was assessed without NMB and with deep NMB [post‐tetanic count (PTC) < 2] with rocuronium. The differences between IAP allowing for an adequate surgical field before and after administration of rocuronium were determined, as were effects of patient gender, age, and body mass index.

Results

Mean IAP without NMB was 12.75 (standard deviation 4.49) mmHg. Immediately after achieving a deep NMB, this was 7.20 (2.51). This pressure difference of 5.55 mmHg (5.08, P < 0.001) dropped to 3.00 mmHg (4.30, P < 0.01) after 15 min. Higher IAP differences were found in women compared with men. A modest inverse relationship was found between pressure difference and age.

Conclusions

We found an almost 25% lower IAP after a deep NMB compared with no block in laparoscopic cholecystectomy. Younger and female patients appear to benefit more from deep neuromuscular blockade to reduce IAP.
Sipping, Drinking, and Early Adolescent Alcohol Consumption: A Cautionary Note
Authors: Wadolowski Monika , Bruno Raimondo , Aiken Alexandra , Stone Chiara , Najman Jake , Kypri Kypros , Slade Tim , Hutchinson Delyse , McBride Nyanda , Mattick Richard P.
Published: February 2015

Background

Epidemiological studies report markedly varying rates of adolescent alcohol involvement. Despite being a common adolescent behavior, a potential cause of this variation is that consumption of sips is either not measured or not distinguished from consumption of whole beverages.

Methods

Participants were 1,843 grade 7 adolescents recruited across 49 Australian secondary schools (M age = 12.4, SD = 0.5). Quantity and frequency of lifetime and past 6‐month consumption were assessed, distinguishing between sipping and drinking. For comparison with international population surveys, quantity was reported as any consumption, sipping only, and drinking only.

Results

Combining sipping and drinking into a single category, lifetime consumption was reported by 67.3% of the present sample. Distinguishing lifetime consumption by sipping and drinking: only 7.8% of adolescents had consumed a whole beverage; the remaining 59.6% had only sipped. Consumption of whole beverages was mostly limited to 1 to 2 drinks (84.2% of drinkers). Sipping and drinking were also infrequent: 78.2% of sipping and 60.4% of drinking, occurred less than monthly. Heavy episodic consumption was uncommon (1.2% of the sample). When other population studies were inspected, a clear trend for higher drinking rates were found in those studies where sipping was counted as drinking and vice versa.

Conclusions

Consumption of whole beverages appears infrequent in early adolescence, as sipping, but not drinking, was common in our sample. Comparing the present data with international population consumption measures highlights the need to more precisely measure and report adolescent consumption, particularly in relation to sipping.
Genetic Absence of nNOS Worsens Fetal Alcohol Effects in Mice. I: Behavioral Deficits
Authors: Karacay Bahri , Bonthius Nancy E. , Plume Jeffrey , Bonthius Daniel J.
Published: February 2015

Background

Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed to alcohol in utero are equally affected by it. While some children have major deficits, others are spared. This unequal vulnerability is likely due largely to differences in fetal genetics. Some fetuses appear to have certain genotypes that make them much more prone to FASD. However, to date, no gene has been identified that worsens alcohol‐induced brain dysfunction. Nitric oxide (NO) is a gaseous molecule that can protect developing neurons against alcohol‐induced death. In the brain, NO is produced by neuronal nitric oxide synthase (nNOS). In this study, we examined whether homozygous mutation of the nNOS gene in mice worsens the behavioral deficits of developmental alcohol exposure.

Methods

Wild‐type and nNOS−/− mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests, including open field activity, the Morris water maze, and paired pulse inhibition.

Results

For the wild‐type mice, alcohol impaired performance only in the water maze. In contrast, for the nNOS−/− mice, alcohol impaired performance on all 3 tasks. Furthermore, the nNOS−/− mice were substantially more impaired than wild‐type mice in their performance on all 3 of the behavioral tests and at both the low (2.2) and high (4.4) doses of alcohol.

Conclusions

Targeted disruption of the nNOS gene worsens the behavioral impact of developmental alcohol exposure and allows alcohol‐induced learning problems to emerge that are not seen in wild type. This is the first demonstration that a specific genotype can interact with alcohol to worsen functional brain deficits in an animal model of FASD.
Prenatal Alcohol Exposure Alters Steady‐State and Activated Gene Expression in the Adult Rat Brain
Authors: Lussier Alexandre A. , Stepien Katarzyna A. , Neumann Sarah M. , Pavlidis Paul , Kobor Michael S. , Weinberg Joanne
Published: February 2015

Background

Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant‐induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE‐induced alterations to their transcriptome may underlie abnormal steady‐state functions and responses to immune challenge. This study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long‐term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females.

Methods

Adult females from PAE, pair‐fed (PF), and ad libitum‐fed control (C) groups were injected with either saline or complete Freund's adjuvant. Animals were terminated at the peak of inflammation or during resolution (Days 16 and 39 postinjection, respectively); cohorts of saline‐injected PAE, PF, and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole‐genome mRNA expression microarrays.

Results

Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline‐injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant‐injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair‐fed animals.

Conclusions

These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long‐term effects of PAE on the central nervous system response under steady‐state conditions and following an inflammatory insult.
Personalized Feedback Based on a Drink‐Pouring Exercise May Improve Knowledge of, and Adherence to, Government Guidelines for Alcohol Consumption
Authors: de Visser Richard O.
Published: February 2015

Background

Although most people are aware of government guidelines for alcohol consumption, few have accurate knowledge of these and fewer still use these guidelines to monitor their drinking. Most people also lack accurate knowledge of the alcohol content of the drinks they consume. The aim of the study reported here was to examine whether or not personalized feedback on alcohol consumption based on performance in a drink‐pouring task and self‐reported alcohol intake would improve university students’ knowledge of alcohol consumption guidelines and reduce their alcohol intake.

Methods

A quasi‐randomized control trial with a 2‐month follow‐up was conducted with 200 students aged 18 to 37 in the south of England. Participants were allocated to a “pour + feedback” group that completed a drink‐pouring task and received personalized feedback, a “pour only” group that completed the drink‐pouring task but did not receive feedback, and a control group.

Results

At follow‐up, participants in the “pour + feedback” group had significantly better knowledge of government guidelines, and significantly lower weekly alcohol intake when compared to the “control” and “pour only” groups.

Conclusions

Further refinement of the drink‐pouring intervention and feedback is reported in this paper, and assessment of their impact in various populations may lead to better understanding of which elements of personalized feedback have the greatest influence on young people's alcohol use.
Association Study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A Polymorphisms with Alcohol Dependence in a Population from Northeastern Brazil
Authors: Vasconcelos Any Carolina C. G. , Neto Edmilson de Souza R. , Pinto Giovanny R. , Yoshioka France Keiko N. , Motta Fábio José N. , Vasconcelos Daniel Fernando P. , Canalle Renata
Published: February 2015

Background

Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD. The aim of this search was to test the association of the SLC6A3 40 bp‐VNTR and DRD2/ANKK1 Taq1A single nucleotide polymorphism (SNP), a transporter and receptor of the dopaminergic system, with AD through a study in a population of northeastern Brazil.

Methods

The study design was a case–control that included 227 males of northeastern Brazil (113 alcoholics and 114 controls). Alcoholics were classified according to the DSM‐IV criteria for AD and controls were subjects who had nonalcohol problems or who never drank. Genotyping was detected through polymerase chain reaction (PCR) for SLC6A3 40 bp‐VNTR and RFLP‐PCR for DRD2/ANKK1 Taq1A, and subsequent electrophoresis on a 2% agarose gel. The distribution of allele and genotype frequencies and association of polymorphisms with AD were assessed by chi‐square, Fisher's exact test, and odds ratio (OR) with a confidence interval of 95% and significance p < 0.05. Data were analyzed on BioEstat 5.3 software.

Results

The SLC6A3 40 bp‐VNTR was associated with AD, allelic, and genotypic frequencies were significantly different, respectively (A9 vs. A10: OR = 1.88; p = 0.01; A9/A9 vs. A10/A10: OR = 6.25; p = 0.02; A9/A9 vs. A9/A10 + A10A10: OR = 5.44; p = 0.03). However, there was no statistically significant difference when the allelic (p = 0.10) and genotypic (p > 0.05) frequencies for DRD2/ANKK1 Taq1A were compared.

Conclusions

These findings suggest that A9 allele and A9/A9 genotype of the SLC6A3 40 bp‐VNTR are involved in the vulnerability to AD in the population studied. However, for the DRD2/ANKK1 SNP does not present contributions to the development of AD.
Gender Effects in Alcohol Dependence: An fMRI Pilot Study Examining Affective Processing
Authors: Padula Claudia B. , Anthenelli Robert M. , Eliassen James C. , Nelson Erik , Lisdahl Krista M.
Published: February 2015

Background

Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing.

Methods

Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole‐brain linear regression analyses were performed, and follow‐up analyses examined whether AD status significantly predicted depressive symptoms and/or coping.

Results

Fearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals.

Conclusions

Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing.