The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions

Finalité et invention : perspectives architecturales et philosophiques

Seit der prominenten Stellung der utilitas in der vitruvianischen Trias wird die Aufgabe von Architektur und ihr Verhältnis zum Entwurf theoretisch reflektiert. Kategorien wie Zweck, Funktion oder commodité bilden dabei ebenso den Kern der Disziplin wie sie zunächst im scheinbaren Widerspruch zu Freiheit und Erfindung stehen. Dieses spannungsreiche Verhältnis manifestiert sich in einer Vielzahl von Gegensätzen: Normierung gegenüber künstlerischer Freiheit – Schaffen von Freiräumen für die Nutzer der Architektur gegenüber dem Ziel einer Prägung des Menschen durch den Architekten – das Abbilden von Formen und Strukturen aus den Bereichen der Natur, Technik oder Ökonomie gegenüber einem schöpferischen Individualismus. Dieses produktive Wechselspiel von Erfindung und Zweck verbindet in selten konsequenter Weise nicht nur die Bereiche Architektur und Philosophie miteinander, sondern auch die Mikro- und Makroebene eines Architekturdiskurses, der sich zwischen Baustelle und theoretischer Reflexion entfaltet.Depuis la célèbre formulation de l’utilitas au sein de la triade vitruvienne, la tâche de l’architecture et sa relation au projet ont fait l’objet d’une réflexion théorique intense. Des catégories telles que la finalité, la fonction ou la commodité forment le cœur de la discipline en même temps qu’elles semblent entrer en contradiction avec la liberté d’invention de l’architecte. Une telle tension se manifeste dans de nombreuses oppositions: normalisation contre liberté artistique; création d’espaces pour le libre usage de l’architecture contre volonté d’imprégnation de l’existence humaine par l’activité de l’architecte; reproduction de formes et de structures issues des domaines de la nature, de la technique et de l’économie contre individualisme créateur. Cette interaction productive entre invention et finalité permet non seulement de relier l’une à l’autre l’architecture et la philosophie, et ce d’une manière particulièrement intéressante, mais également les niveaux microscopiques et macroscopiques du discours architectural, qui se déploient entre le travail constructif sur le chantier et la réflexion théorique

The Drinker’s Effect on the Social Environment: A Conceptual Framework for Studying Alcohol’s Harm to Others

The paper considers conceptual and methodological issues in studying the scope of alcohol’s harm to others. Reasons are suggested for the relative neglect of the topic. The approaches in two relevant research traditions are considered: population surveys on alcohol problems, and economic cost of alcohol studies. Ways of conceptualizing and measuring aspects of the drinker’s effects on others are considered, in terms of main types of relationship with the other, and in terms of major societal response institutions. The main types of data tend to measure different levels of severity, with population survey data dominated by less severe problems, and response institution data by more severe problems; so both are needed for a three-dimensional view. Research questions for the field and its policy significance are noted

Genomewide identification of \u3ci\u3ePseudomonas syringae\u3c/i\u3e pv.\u3ci\u3etomato\u3c/i\u3e DC3000 promoters controlled by the HrpL alternative sigma factor

The ability of Pseudomonas syringae pv. tomato DC3000 to parasitize tomato and Arabidopsis thaliana depends on genes activated by the HrpL alternative sigma factor. To support various functional genomic analyses of DC3000, and specifically, to identify genes involved in pathogenesis, we developed a draft sequence of DC3000 and used an iterative process involving computational and gene expression techniques to identify virulence-implicated genes downstream of HrpLresponsive promoters. Hypersensitive response and pathogenicity (Hrp) promoters are known to control genes encoding the Hrp (type III protein secretion) machinery and a few type III effector proteins in DC3000. This process involved (i) identification of 9 new virulenceimplicated genes in the Hrp regulon by miniTn5gus mutagenesis, (ii) development of a hidden Markov model (HMM) trained with known and transposon-identified Hrp promoter sequences, (iii) HMM identification of promoters upstream of 12 additional virulence-implicated genes, and (iv) microarray and RNA blot analyses of the HrpLdependent expression of a representative subset of these DC3000 genes. We found that the Hrp regulon encodes candidates for 4 additional type III secretion machinery accessory factors, homologs of the effector proteins HopPsyA, AvrPpiB1 (2 copies), AvrPpiC2, AvrPphD (2 copies), AvrPphE, AvrPphF, and AvrXv3, and genes associated with the production or metabolism of virulence factors unrelated to the Hrp type III secretion system, including syringomycin synthetase (SyrE), N-(indole-3-acetyl)-L-lysine synthetase (IaaL), and a subsidiary regulon controlling coronatine production. Additional candidate effector genes, hopPtoA2, hopPtoB2, and an avrRps4 homolog, were preceded by Hrp promoter-like sequences, but these had HMM expectation values of relatively low significance and were not detectably activated by HrpL

ART Suppresses Plasma HIV-1 RNA to a Stable Set Point Predicted by Pretherapy Viremia

Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia suppressed to less than 50–75 copies/ml on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-1 RNA with a limit of detection of one copy of HIV-1 RNA. Single copy assay results revealed that >80% of patients on initial antiretroviral therapy for 60 wk had persistent viremia of one copy/ml or more with an overall median of 3.1 copies/ml. The level of viremia correlated with pretherapy plasma HIV-1 RNA but not with the specific treatment regimen. Longitudinal studies revealed no significant decline in the level of viremia between 60 and 110 wk of suppressive antiretroviral therapy. These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy

Impact of the WHO “best buys” for alcohol policy on consumption and health in the Baltic countries and Poland 2000–2020

Funding Information: Funding: Research reported in this publication was in part supported by the (U.S.) National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH), grant number 1R01AA028224 . This research was conducted as part of the project ‘Evaluation of the impact of alcohol control policies on morbidity and mortality in Lithuania and other Baltic states’ and we would like to thank the whole team for their input to wider discussions in generating the research reported in this paper. Content is the responsibility of the authors and does not reflect official positions of the NIAAA or the NIH. Publisher Copyright: © 2023Alcohol use is a major risk factor for burden of disease. This narrative review aims to document the effects of major alcohol control policies, in particular taxation increases and availability restrictions in the three Baltic countries (Estonia, Latvia, and Lithuania) between 2000 and 2020. These measures have been successful in curbing alcohol sales, in general without increasing consumption of alcoholic beverages from unrecorded sources; although for more recent changes this may have been partly due to the COVID-19 pandemic. Moreover, findings from time-series analyses suggest improved health, measured as reductions in all-cause and alcohol-attributable mortality, as well as narrowing absolute mortality inequalities between lower and higher educated groups. For most outcomes, there were sex differences observed, with alcohol control policies more strongly affecting males. In contrast to this successful path, alcohol control policies were mostly dismantled in the neighbouring country of Poland, resulting in a rising death toll due to liver cirrhosis and other alcohol-attributable deaths. The natural experiment in this region of high-income European countries with high consumption levels highlights the importance of effective alcohol control policies for improving population health.Peer reviewe

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

<p>Abstract</p> <p>Background</p> <p>In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.</p> <p>Methods</p> <p>A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.</p> <p>Results</p> <p>There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.</p> <p>Conclusion</p> <p>The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.</p

Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease

Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease