A combined intervention strategy to increase linkage to and retention in substance use treatment for individuals accessing hospital-based services: study protocol.

Background: In 2020, New Mexico had the highest alcohol related death and the 11th highest drug overdose rate in the U.S. Towards the long-term goal of addressing this public health problem, we are implementing and evaluating an multi-level intervention designed to identify adults at risk of substance use disorder (SUD) and encourage linkage to and retention in treatment. The first level includes equipping the ED and medical inpatient units of a safety-net hospital with a method to screen individuals at risk of a SUD. The second level includes Seeking Safety (SS), a trauma-specific treatment for PTSD and SUD; and pharmacotherapy for SUD. Motivational Interviewing (MI) is used throughout both levels. Using the SPIRIT guidelines and checklist, this study protocol describes the multi-level intervention and the methodology we are using to assess feasibility and effectiveness. Methods: We are using a Type 1 hybrid implementation design with a non-randomized approach (ISRCTN registration # ISRCTN33100750). We aim to enroll 110 adults ( ≧ 18 ) who screen positive for unhealthy use of alcohol, prescription medications (used nonmedically) and/or illicit drugs. Peer support workers are responsible for screening, using MI to increase engagement in screening and treatment and delivery of SS. Pharmacotherapy is provided by addiction clinical specialists. Treatment is provided post hospital discharge via telehealth to increase access to care. Participants are identified through (1) review of electronic health records for individuals with a chief or secondary complaint or mental health condition relating to alcohol and/or other drug use, (2) referrals from clinical staff and (3) screening in the ED and medical inpatient units. Feasibility is being measured through process data. Effectiveness will be determined by changes in two primary outcomes: (i) PTSD symptom severity; and (ii) substance use. Discussion: Our study will expand on research related to the implementation of treatment strategies for patients presenting at EDs and admitted to medical inpatients units wherein there is a significant window of opportunity to link patients with follow-up behavioral and clinical services for alcohol and/or drug misuse. The challenges associated with implementation and strategies that have been helpful to address these challenges will further inform the field.

First report of Central-line-associated bloodstream infection (CLAB- SI) due to Enterococcus raffinosus (ER) in a cancer patient.

Abstract: Despite the advances made by therapeutic technologies, healthcare-associated infections (HAIs) are currently still a worldwide problem. Central-line-associated bloodstream infections (CLABSIs) are one of the most common causes of HAIs. The cost of CLABSIs is considerable, both for the increase in morbidity and financial resources expenses. Coagulase-negative staphylococci are the common pathogens responsible for CLABSIs, followed by Staphylococcus aureus, Enterococci, and Candida spp. The Enterococcus genus comprises of more than 50 species but E. faecalis and E. faecium are the most common causes of infections in humans. Enterococcus Raffinosus (ER) is a non-faecalis and non-faecium enterococcus even if ER has rarely been proven to be a human pathogen, recent reports of infections caused by enterococci that are relatively resistant to beta-lactam antibiotics by non-p-lactamase mechanisms have included strains of ER. Here we describe a first report of CLABSI due to Enterococcus Raffinosus in a cancer patient.

Magnesium alginate in patients with laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a common disease caused by the leaking beck of gastric material out of the esophagus. The main symptoms are dysphonia, dysphagia, and cough. There is an established use of proton pump inhibitors (PPI) in patients with suspected LPR in common practice. This habit is translated by the standard strategy to use PPI in treating patients with gastroesophageal reflux. However, PPI can not wholly inhibit all types of reflux and are burden by adverse effects. Alginate, a derivative from algae, is devoid of side effects and effectively counteracts gastric material reflux forming a foaming gel in the stomach. The current study enrolled 100 outpatients with LPR. Alginate treatment was administered for two months. Patients underwent four visits (at baseline and 15, 30, and 60 days after treatment). A visual analog scale assessed the perception of dysphonia, dysphagia, and cough. Alginate significantly (p<0.0001) reduced all parameters. Therefore, the current study demonstrated that magnesium alginate was effective and safe in LPR treatment.

Derivation of the spin-glass order parameter from stochastic thermodynamics.

A fluctuation relation is derived to extract the order parameter function q(x) in weakly ergodic systems. The relation is based on measuring and classifying entropy production fluctuations according to the value of the overlap q between configurations. For a fixed value of q, entropy production fluctuations are Gaussian distributed allowing us to derive the quasi-FDT so characteristic of aging systems. The theory is validated by extracting the q(x) in various types of glassy models. It might be generally applicable to other nonequilibrium systems and experimental small systems.

Heat fluctuations of Brownian oscillators in nonstationary processes: Fluctuation theorem and condensation transition.

We study analytically the probability distribution of the heat released by an ensemble of harmonic oscillators to the thermal bath, in the nonequilibrium relaxation process following a temperature quench. We focus on the asymmetry properties of the heat distribution in the nonstationary dynamics, in order to study the forms taken by the fluctuation theorem as the number of degrees of freedom is varied. After analyzing in great detail the cases of one and two oscillators, we consider the limit of a large number of oscillators, where the behavior of fluctuations is enriched by a condensation transition with a nontrivial phase diagram, characterized by reentrant behavior. Numerical simulations confirm our analytical findings. We also discuss and highlight how concepts borrowed from the study of fluctuations in equilibrium under symmetry-breaking conditions [Gaspard, J. Stat. Mech. (2012) P0802110.1088/1742-5468/2012/08/P08021] turn out to be quite useful in understanding the deviations from the standard fluctuation theorem.

General phase diagram of multimodal ordered and disordered lasers in closed and open cavities.

We present a unified approach to the theory of multimodal laser cavities including a variable amount of structural disorder. A general mean-field theory is studied for waves in media with variable nonlinearity and randomness. Phase diagrams are reported in terms of optical power, degree of disorder, and degree of nonlinearity, tuning between closed and open cavity scenarios. In the thermodynamic limit of infinitely many modes, the theory predicts four distinct regimes: a continuous wave behavior for low power, a standard mode-locking laser regime for high power and weak disorder, a random laser for high pumped power and large disorder, and a novel intermediate regime of phase locking occurring in the presence of disorder but below the lasing threshold.

Small-cluster renormalization group in Ising and Blume-Emery-Griffiths models with ferromagnetic, antiferromagnetic, and quenched disordered magnetic interactions.

The Ising and Blume-Emery-Griffiths (BEG) models' critical behavior is analyzed in two dimensions and three dimensions by means of a renormalization group scheme on small clusters made of a few lattice cells. Different kinds of cells are proposed for both ordered and disordered model cases. In particular, cells preserving a possible antiferromagnetic ordering under renormalization allow for the determination of the Néel critical point and its scaling indices. These also provide more reliable estimates of the Curie fixed point than those obtained using cells preserving only the ferromagnetic ordering. In all studied dimensions, the present procedure does not yield a strong-disorder critical point corresponding to the transition to the spin-glass phase. This limitation is thoroughly analyzed and motivated.

Fluctuation relation for weakly ergodic aging systems.

A fluctuation relation for aging systems is introduced and verified by extensive numerical simulations. It is based on the hypothesis of partial equilibration over phase-space regions in a scenario of entropy-driven relaxation. The relation provides a simple alternative method, amenable of experimental implementation, to measure replica symmetry breaking parameters in aging systems. The connection with the effective temperatures obtained from the fluctuation-dissipation theorem is discussed.

Influence of infection on malaria-specific antibody dynamics in a cohort exposed to intense malaria transmission in northern Uganda.

The role of submicroscopic infections in modulating malaria antibody responses is poorly understood and requires longitudinal studies. A cohort of 249 children ≤5 years of age, 126 children between 6 and 10 years and 134 adults ≥20 years was recruited in an area of intense malaria transmission in Apac, Uganda and treated with artemether/lumefantrine at enrolment. Parasite carriage was determined at enrolment and after 6 and 16 weeks using microscopy and PCR. Antibody prevalence and titres to circumsporozoite protein, apical membrane antigen-1 (AMA-1), merozoite surface protein-1 (MSP-119 ), merozoite surface protein-2 (MSP-2) and Anopheles gambiae salivary gland protein 6 (gSG6) were determined by ELISA. Plasmodium falciparum infections were detected in 38·1% (194/509) of the individuals by microscopy and in 57·1% (284/493) of the individuals by PCR at enrolment. Antibody prevalence and titre against AMA-1, MSP-119 , MSP-2 and gSG6 were related to concurrent (sub-)microscopic parasitaemia. Responses were stable in children who were continuously infected with malaria parasites but declined in children who were never parasitaemic during the study or were not re-infected after treatment. These findings indicate that continued malaria infections are required to maintain antibody titres in an area of intense malaria transmission.

Nonequilibrium and information: the role of cross correlations.

We discuss the relevance of information contained in cross correlations among different degrees of freedom, which is crucial in nonequilibrium systems. In particular we consider a stochastic system where two degrees of freedom X{1} and X{2}-in contact with two different thermostats-are coupled together. The production of entropy and the violation of equilibrium fluctuation-dissipation theorem (FDT) are both related to the cross correlation between X{1} and X{2}. Information about such cross correlation may be lost when single-variable reduced models for X_{1} are considered. Two different procedures are typically applied: (a) one totally ignores the coupling with X{2}; and (b) one models the effect of X{2} as an average memory effect, obtaining a generalized Langevin equation. In case (a) discrepancies between the system and the model appear both in entropy production and linear response; the latter can be exploited to define effective temperatures, but those are meaningful only when time scales are well separated. In case (b) linear response of the model well reproduces that of the system; however the loss of information is reflected in a loss of entropy production. When only linear forces are present, such a reduction is dramatic and makes the average entropy production vanish, posing problems in interpreting FDT violations.

Statistical mechanical approach to secondary processes and structural relaxation in glasses and glass formers: a leading model to describe the onset of Johari-Goldstein processes and their relationship with fully cooperative processes.

The interrelation of dynamic processes active on separated time-scales in glasses and viscous liquids is investigated using a model displaying two time-scale bifurcations both between fast and secondary relaxation and between secondary and structural relaxation. The study of the dynamics allows for predictions on the system relaxation above the temperature of dynamic arrest in the mean-field approximation, that are compared with the outcomes of the equations of motion directly derived within the Mode Coupling Theory (MCT) for under-cooled viscous liquids. By varying the external thermodynamic parameters, a wide range of phenomenology can be represented, from a very clear separation of structural and secondary peak in the susceptibility loss to excess wing structures.

Thermodynamic first order transition and inverse freezing in a 3D spin glass.

We present a numerical study of the random Blume-Capel model in three dimensions. The phase diagram is characterized by spin-glass-paramagnet phase transitions of both first and second order in the thermodynamic sense. Numerical simulations are performed using the exchange Monte Carlo algorithm, providing clear evidence for inverse freezing. The main features at criticality and in the phase coexistence region are investigated. We are not privy to other 3D short-range systems with quenched disorder undergoing inverse freezing.

A protein microarray immunoassay for the serological evaluation of the antibody response in vertically transmitted infections.

The detection of specific serum antibodies is mainly achieved by enzyme-linked immunosorbent assay (ELISA). Here, we describe the setting up of a microarray-based serological assay to screen for IgG and IgM against vertically transmitted pathogens (Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, Chlamydia trachomatis). The test, accommodated onto a restricted area of a microscope slide, consists of: (a) the immobilization of antigens and human IgG and IgM antibody dilution curves, laid down in an orderly manner; (b) addition of serum samples; (c) detection of antigen-serum antibodies complexes by indirect immunofluorescence. The IgG and IgM curves provide an internal calibration system for the interpolation of the signals from the single antigens. The test was optimized in terms of spotting conditions and processing protocol. The detection limit was 400 fg for the IgG assay and 40 fg for the IgM assay; the analytical specificity was >98%. The clinical sensitivity returned an average value of 78%, the clinical specificity was >96%, the predictive values were >73%, and the efficiency was >88%. The results obtained make this test a promising tool, suitable for introduction in the clinical diagnostic routine of vertically transmitted infections, in parallel (and in future as an alternative) to ELISA.

[Efficacy of inhalation therapy with water of Salsomaggiore (Italy) in chronic and recurrent nasosinusal inflammation treatment]. / Effetti terapeutici dell'acqua termale salsobromoiodica di Salsomaggiore nel trattamento delle fl ogosi naso-sinusali ricorrenti e croniche.

OBJECTIVES: Aim of the research was the demonstration of the efficacy of thermal water vs saline in the recurrent and chronic nasosinusal pathologies treatment. MATERIALS AND METHODS: 120 patients randomized into 2 groups of 60 subjects each, all affected by recurrent or chronic rhinosinusitis with/without I degree nasal polyposis. At the beginning and at the end of the study, in all the subjects the clinical history, objective examination and the instrumental analysis of nasal functions by active anterior rhinometry, acustic rhinometry, nasal mucociliary transport time determination and nasal mucosa scraping were performed. Patients of the study group underwent crenotherapy treatment (vapour inhalation, aerosol and nasal douching) with thermal water for 14 days at Salsomaggiore Thermal baths. Other patients underwent nasal douching and aerosol with saline twice a day for 14 days at the Rhinologic Centre of the ENT Clinic of Siena University. RESULTS: At the end of the study, only the patients undergone to crenothrapic treatment with salt-bromine-iodic water showed a significant improvement of nasal obstruction, rinorrea and number of nocturnal arousals. The improvement, even if present, was not significant in the control group. Same positive variations were observed concerning nasal mucosa congestion, nasal secretion and mucociliary transport time reaching the significance in the study group. CONCLUSIONS: Crenotherapy with salt-bromine-iodic water should be considered as efficacious therapeutic tool in the management of chronic and recurrent rhinosinusitis.

[Glucan solution nasal spray vs saline in the treatment of chronic rhinosinusitis: a multi-centric double blind randomised clinical trial]. / Soluzione spray nasale di glucano vs soluzione fisiologica nel trattamento della rinosinusite cronica: studio multicentrico in doppio cieco randomizzato.

OBJECTIVES: The aim of our study was to evaluate the efficacy of 30 days treatment with glucan solution nasal spray vs. saline in the treatment of signs and symptoms of chronic rhinosinusitis. MATERIALS AND METHODS: 100 patients affected by chronic rhinosinusitis were enrolled. At the beginning and at the end of the study were evaluated: nasal congestion, headache, rhinorrea, facial pain, rhinopharyngeal exudate, inferior turbinate hypertrophy; a complete instrumental analysis of nasal functions by Active Anterior Rhinomanometry, nasal Muco-Ciliary Transport time and scraping of nasal mucosa was also performed. The patients were randomized 1:1 for receiving intranasal saline or intranasal glucan solution spray. Treatment was administered as follows: 2 puffs/nostril 3 times a day for 30 days. RESULTS: The patients in therapy with the glucan solution showed a significant improvement concerning rhinorrea facial pain, intensity of headache, inferior turbinate hypertrophy, rhinopharyngeal exudates, inspiratory/expiratory nasal resistences, Muco-ciliary transport time, normalization of nasal mucosas and rhinocytogram; saline lavage didn't show this effects. Both treatment improved rhinorrea, instead both treatment didn't affect nasal congestion. CONCLUSIONS: According to the results of our multicentric double blind randomized study, we suggest the use of glucan solution nasal spray as an efficacious therapeutic tool in the management of nasal symptoms in patients affected by chronic rhinosinusitis.

Functional gastrointestinal disorders in migrainous children: efficacy of flunarizine.

The aim of this study was to evaluate the prevalence of functional gastrointestinal disorders (FGIDs) in children with migraine headache and the effects of flunarizine on gastrointestinal manifestations. We studied 50 migrainous children (mean age 8.63 years). The clinical pattern and the diagnosis of FGIDs were obtained from structured questionnaires. All subjects underwent measurement of total gastric emptying time (TGEt) performed by real-time ultrasonography of the gastric antrum at baseline (T0). In the second part of the study, we evaluated 10 migrainous children (mean age 9.8 years) with associated FGIDs. In these 10 patients, repeated TGEt evaluation together with a detailed symptom history was obtained after 1 (T1) and 2 months (T2) of treatment with flunarizine. Control groups were composed of 10 migrainous children without FGIDs (mean age 9.2 years) and nine sex- and age-matched healthy children. Gastrointestinal disorders were present in 70% of the patients. Migrainous children with FGIDs had significantly (P < 0.01) more prolonged TGEt than subjects without FGIDs. Prior to therapy, all migrainous children with FGIDs had prolongation of TGEt compared with controls (P < 0.05). Patients on flunarizine had a significant decrease in TGEt at both 1 (P < 0.01) and 2 months (P = 0.002) of therapy. The mean frequency of abdominal pain per month was significantly (P < 0.001) reduced at T1 compared with T0. The mean frequency of vomiting per month was significantly decreased at T1 (P < 0.05) and even more so at T2 (P < 0.01). Finally, the mean frequency of headache per month was significantly reduced only at T2 (P < 0.05), whereas the mean duration of headache was significantly decreased at T1 (P < 0.01) with no difference between T1 and T2. Most children with migraine report FGIDs, associated with a delayed gastric emptying. Flunarizine decreases the frequency and duration of migrainous episodes as well as the gastrointestinal symptoms.

Spherical 2 + p spin-glass model: an exactly solvable model for glass to spin-glass transition.

We present the full phase diagram of the spherical 2 + p spin-glass model with p > or = 4. The main outcome is the presence of a phase with both properties of full replica symmetry breaking phases of discrete models, e.g., the Sherrington-Kirkpatrick model, and those of one replica symmetry breaking. This phase has a finite complexity which leads to different dynamic and static properties. The phase diagram is rich enough to allow the study of different kinds of glass to spin glass and spin glass to spin glass phase transitions.

Spin-glass complexity.

We study the quenched complexity in spin-glass mean-field models satisfying the Becchi-Rouet-Stora-Tyutin supersymmetry. The outcome of such study, consistent with recent numerical results, allows, in principle, to conjecture the absence of any supersymmetric contribution to the complexity in the Sherrington-Kirkpatrick model. The same analysis can be applied to any model with a full replica symmetry breaking phase, e.g., the Ising p-spin model below the Gardner temperature. The existence of different solutions, breaking the supersymmetry, is also discussed.

Serodiagnosis of infectious diseases with antigen microarrays.

AIMS: To generate protein microarrays by printing microbial antigens on slides to enable the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus (HSV) types 1 and 2. METHODS AND RESULTS: Antigens were printed on activated glass slides using high-speed robotics. The slides were incubated with serum samples and subsequently with fluorescently labelled secondary antibodies. Human IgG and IgM bound to the printed antigens were detected using confocal scanning microscopy and quantified with internal calibration curves. The microarray assay could detect as little as 0.5 pg of both IgG and IgM bound onto the glass surface. Precision profiles ranged from 1.7 to 18.5% for all the antigens. Microarrays and commercial ELISAs were utilized to detect serum antibodies against the ToRCH antigens in a panel of characterized human sera. Overall >80% concordance was obtained between microarray and ELISA kits in the classification of sera. CONCLUSIONS: These results indicate that the microarray is a suitable assay format for the serodiagnosis of infectious diseases. SIGNIFICANCE AND IMPACT OF STUDY: Antigen microarrays can be optimized for clinical use, their performance is equivalent to ELISA but they offer significant advantages in throughput, convenience and cost.