Managing acutely aggressive or agitated people in a psychiatric setting: a survey in Lebanon

Background: Violent patients constitute 10% of all psychiatric admissions. Treatment options and clinical practice interventions vary across the globe and no survey of practice in a Middle Eastern setting exists. Surveying treatments in Lebanon will show treatment interventions used in this part of the world and, most importantly, provide the treatment options that could potentially be used for clinical trials pertaining to emergency psychiatry. Methods: A survey of clinicians’ opinions and practice was conducted between July and August 2017 at the largest psychiatric hospital in Lebanon. Results: Five of seven experienced psychiatrists provided opinions when interviewed of their preferred intervention when dealing with an emergency psychiatric episode. Whilst this varied in detail, there was a consistent view that there should first be verbal control, then use of medications, and finally physical restrain of the patient. A total of 39 emergency episodes (28 people) occurred in the one month (64% men in their 30s). Bipolar disorder was the most frequent single diagnosis behind the aggression (n=16, 41%; 12 people 43%) but the combined schizophrenia-like illnesses underlay 18 of the 39 episodes (46%; 13/28 people 46%). In clinical life, we found evidence of high family involvement, but little attempts made at initial verbal control in the hospital. All 39 episodes involved administration of pharmacological interventions. Medications were used in 29 of cases (74%) and non-medication interventions used in the remaining 10/39 (26%). Conclusion: This survey provides some evidence that clinicians’ preferences may not fully reflect clinical practice but also that experienced clinicians are using several clearly effective techniques to manage these very difficult situations. However, as for other parts of the world, treatment in Lebanon has limited or no underpinning by evidence from well-designed, conducted and reported evaluative studies

Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes

Previous studies suggest that sarcolemmal potassium currents play important roles in cardiac hypertrophy. IGF-1 contributes to cardiac hypertrophy via activation of PI3K/Akt signaling. However, the relationships between IGF-1, PI3K/Akt signaling and sarcolemmal potassium currents remain unknown. Therefore, we tested the hypothesis that IGF-1 and PI3K/Akt signaling, independently, decrease sarcolemmal potassium currents in cardiac myocytes of neonatal rats. We compared the delayed outward rectifier (IK) and the inward rectifier (IK) current densities resulting from IGF-1 treatments to those resulting from simulation of PI3K/Akt signaling using adenoviral (Ad) BD110 and wild-type Akt and to those resulting from inhibition of PI3K signaling by LY294002. Ad.BD110 and Ad.Akt decreased IK and these decrements were attenuated by LY 294002. The IGF-1 treatments decreased both IK and IK1 but only the IK decrement was attenuated by LY294002. These findings demonstrate that IGF-1 may contribute to cardiac hypertrophy by PI3K/Akt signal transduction mechanisms in neonatal rat cardiomyocytes. Failure of LY294002 to effectively antagonize IGF-1 induced decrements in IK1 suggests that a signal pathway adjunct to PI3K/Akt contributes to IGF-1 protection against arrhythmogenesis in these myocytes. Our findings imply that sarcolemmal outward and inward rectifier potassium channels are substrates for IGF-1/PI3K/Akt signal transduction molecules

Low Alcohol Beneficial Effects on the Cardiac Function During Cardiac Hypertrophy

Chronic low alcohol exposure has been shown clinically to have beneficial cardiac effects; whereas chronic high alcohol consumption can lead to heart failure. We have previously shown that cardiac inotropy is closely related to the activation of the survival PI3K/Akt. This study aimed to determine the effects of chronic low and high alcohol on cardiac function as well as to determine if low alcohol can alleviate the development of volume-overload-dependent (shunt) cardiac hypertrophy. Littermate adult rats were put on a 3-months isocaloric Lieber-Decarli liquid diet with either low alcohol (LA: 5mM) or high alcohol (HA: 100mM) levels. The rats were further divided into sham or shunted group. The measured final blood alcohol concentrations were 0.02% and 0.20% respectively. In vivo intra-ventricular catheterization (Scisense/iWorks) of the left ventricle (LV) showed that an improved LV contractility and ejection fraction of the LA group while the opposite occurred with the HA group. Since we currently do not have all experimental results, our partial results show that shunted rats developed eccentric cardiac hypertrophy as expected, which was exacerbated by high alcohol consumption, whereas low alcohol seems to alleviate the effect of volume-overload on the cardiac function to a certain extent. The results of the present study suggest that there is an association between alcohol intake and cardiac function; chronic low alcohol exposure seems to have beneficial cardiac effects; whereas chronic high alcohol consumption is associated with reduced cardiac contractile function and could lead to heart failure over the time

Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV

With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s–601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245–50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk

Effects of Dietary Nitrates on Systemic and Cerebrovascular Hemodynamics

Cerebral blood flow dysregulation is often associated with hypertension. We hypothesized that a beetroot juice (BRJ) treatment could decrease blood pressure and cerebrovascular resistance (CVR). We subjected 12 healthy females to control and BRJ treatments. Cerebrovascular resistance index (CVRI), systolic blood pressure (SBP), total vascular resistance (TVR), and the heart rate-systolic pressure product (RPP) measured at rest and at two exercise workloads were lower after the BRJ treatment. CVRI, SBP, and RPP were lower without a lower TVR at the highest exercise level. These findings suggest improved systemic and cerebral hemodynamics that could translate into a dietary treatment for hypertension

Study protocol for a randomised controlled trial of haloperidol plus promethazine plus chlorpromazine versus haloperidol plus promethazine for rapid tranquilisation for agitated psychiatric patients in the emergency setting (TREC-Lebanon)

Background: Agitated and aggressive behaviours are common in the psychiatric setting and rapid tranquilisation is sometimes unavoidable. A survey of Lebanese practice has shown that an intramuscular haloperidol, promethazine and chlorpromazine combination is a preferred form of treatment but there are no randomised trials of this triple therapy.Methods: This is a pragmatic randomised trial. Setting - the psychiatric wards of the Psychiatric Hospital of the Cross, Jal Eddib, Lebanon. Participants - any adult patient in the hospital who displays an aggressive episode for whom rapid tranquilisation is unavoidable, who has not been randomised before, for whom there are no known contraindications. Randomisation – stratified (by ward) randomisation and concealed in closed opaque envelope by independent parties. Procedure – if the clinical situation arises requiring rapid tranquilisation, medical residents overseeing the patient will open a TREC-Lebanon envelope in which will be notification of which group of treatments should be preferred [Haloperidol + Promethazine + Chlorpromazine (HPC) or Haloperidol + Promethazine (HP)], along with forms for primary, secondary and serious adverse effects. Treatment is not given blindly. Outcome - primary outcome is calm or tranquil at 20 minutes post intervention. Secondary outcomes are calm/tranquil at 40, 60 and 120 minutes post intervention, asleep, adverse effects, use of straitjacket and leaving the ward. Follow-up will be up to two weeks post randomisation.Discussion: Findings from this study will compare the HPC versus HP combination used in Lebanon’s psychiatry emergency routine practice.Trial registration: ClinicalTrials.gov NCT03639558. Registration date, August 21, 2018

Human Cardiac-Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Sex-Related Differences

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Combinations of single-top-quark production cross-section measurements and vertical bar f(LV)V(tb)vertical bar determinations at root s=7 and 8 TeV with the ATLAS and CMS experiments

This paper presents the combinations of single-top-quark production cross-section measurements by the ATLAS and CMS Collaborations, using data from LHC proton-proton collisions at = 7 and 8 TeV corresponding to integrated luminosities of 1.17 to 5.1 fb(-1) at = 7 TeV and 12.2 to 20.3 fb(-1) at = 8 TeV. These combinations are performed per centre-of-mass energy and for each production mode: t-channel, tW, and s-channel. The combined t-channel cross-sections are 67.5 +/- 5.7 pb and 87.7 +/- 5.8 pb at = 7 and 8 TeV respectively. The combined tW cross-sections are 16.3 +/- 4.1 pb and 23.1 +/- 3.6 pb at = 7 and 8 TeV respectively. For the s-channel cross-section, the combination yields 4.9 +/- 1.4 pb at = 8 TeV. The square of the magnitude of the CKM matrix element V-tb multiplied by a form factor f(LV) is determined for each production mode and centre-of-mass energy, using the ratio of the measured cross-section to its theoretical prediction. It is assumed that the top-quark-related CKM matrix elements obey the relation |V-td|, |V-ts| << |V-tb|. All the |f(LV)V(tb)|(2) determinations, extracted from individual ratios at = 7 and 8 TeV, are combined, resulting in |f(LV)V(tb)| = 1.02 +/- 0.04 (meas.) +/- 0.02 (theo.). All combined measurements are consistent with their corresponding Standard Model predictions.Peer reviewe