Alcohol Use Disorder in the Age of Technology: A Review of Wearable Biosensors in Alcohol Use Disorder Treatment

Biosensors enable observation and understanding of latent physiological occurrences otherwise unknown or invasively detected. Wearable biosensors monitoring physiological constructs across a wide variety of mental and physical health conditions have become an important trend in innovative research methodologies. Within substance use research, explorations of biosensor technology commonly focus on identifying physiological indicators of intoxication to increase understanding of addiction etiology and to inform treatment recommendations. In this review, we examine the state of research in this area as it pertains to treatment of alcohol use disorders specifically highlighting the gaps in our current knowledge with recommendations for future research. Annually, alcohol use disorders affect approximately 15 million individuals. A primary focus of existing wearable technology-based research among people with alcohol use disorders is identifying alcohol intoxication. A large benefit of wearable biosensors for this purpose is they provide continuous readings in a passive manner compared with the gold standard measure of blood alcohol content (BAC) traditionally measured intermittently by breathalyzer or blood draw. There are two primary means of measuring intoxication with biosensors: gait and sweat. Gait changes have been measured via smart sensors placed on the wrist, in the shoe, and mobile device sensors in smart phones. Sweat measured by transdermal biosensors detects the presence of alcohol in the blood stream correlating to BAC. Transdermal biosensors have been designed in tattoos/skin patches, shirts, and most commonly, devices worn on the ankle or wrist. Transdermal devices were initially developed to help monitor court-ordered sobriety among offenders with alcohol use disorder. These devices now prove most useful in continuously tracking consumption throughout clinical trials for behavioral treatment modalities. More recent research has started exploring the uses for physical activity trackers and physiological arousal sensors to guide behavioral interventions for relapse prevention. While research has begun to demonstrate wearable devices\u27 utility in reducing alcohol consumption among individuals aiming to cutdown on their drinking, monitoring sustained abstinence in studies exploring contingency management for alcohol use disorders, and facilitating engagement in activity-based treatment interventions, their full potential to further aid in understanding of, and treatment for, alcohol use disorders has yet to be explored

Addressing Positive Suicide Screens in the Emergency Department: The Importance of Post-Discharge Follow-up

Suicide is the tenth leading cause of death and many of those who die by suicide have visited an emergency department (ED) in the months prior to their death. Thus, identification and treatment of suicidal ideation (SI) in the ED is essential to suicide prevention efforts. Although a recent effort to implement universal SI screening has identified more patients with suicide risk, there are still barriers to further risk assessment and intervention, including: patients being too ill, language differences, physician caseload, length of SI evaluation and intervention, staff availability and communication with emergency mental health (EMH) services, and stigma surrounding risk responsibility. To address these issues following the Zero Suicide Model, in November 2017 the pre-existing Behavioral Health Service (BHS) expanded their care to this population, improved communication with EMH to reduce patient burden, and implemented a follow-up call system to contact patients within 48 hours post-discharge. Since November, 61 patients were identified as not receiving further SI evaluation or resources while in the ED. Twenty-four (39.3%) of these patients were successfully contacted by phone, with 15 (62.5%) receiving resources and 9 (37.5%) declining resources due to existing services. All patients with available addresses (86.8%) were sent Caring Contact Cards with information on suicide hotlines and psychiatric emergency services. By attempting calls multiple times, mailing resources, and being brief, yet detailed when evaluating, more patients\u27 SI needs are being treated. The ultimate goal is to provide services to all patients who screen positive for suicide risk presenting to the ED

Dark Energy and Modified Gravity

Despite two decades of tremendous experimental and theoretical progress, the riddle of the accelerated expansion of the Universe remains to be solved. On the experimental side, our understanding of the possibilities and limitations of the major dark energy probes has evolved; here we summarize the major probes and their crucial challenges. On the theoretical side, the taxonomy of explanations for the accelerated expansion rate is better understood, providing clear guidance to the relevant observables. We argue that: i) improving statistical precision and systematic control by taking more data, supporting research efforts to address crucial challenges for each probe, using complementary methods, and relying on cross-correlations is well motivated; ii) blinding of analyses is difficult but ever more important; iii) studies of dark energy and modified gravity are related; and iv) it is crucial that R&D for a vibrant dark energy program in the 2030s be started now by supporting studies and technical R&D that will allow embryonic proposals to mature. Understanding dark energy, arguably the biggest unsolved mystery in both fundamental particle physics and cosmology, will remain one of the focal points of cosmology in the forthcoming decade.Comment: 5 pages + references; science white paper submitted to the Astro2020 decadal surve

Emergency Department Super-utilizer Program Involvement: Pilot Data and Methods Challenges

Super-utilizers are patients who use extreme amounts of medical services, often due to comorbid medical, social, and mental health issues. The MyLink Evaluation Project (MEP) studies MyLink, a program that connects super-utilizers with community support workers (CSWs) to improve the patient experience and reduce costs. The MEP-eligible population is ≥18 years old with at least 5 Emergency Department (ED) visits within 12 months and no other exclusions (e.g., language barriers, living out-of-region). During MEP’s pilot, among 58 eligible patients, 28 consented to being referred to MyLink and followed up. Of these, 7 could not be located for follow-up, 8 refused enrollment, and the remaining 13 enrolled and “engaged” (had at least 3 face-to-face contacts and developed an initial plan). All 13 enrollees were followed at 6 months vs. 4 of the 8 not enrolled. Consequently, we expect about 50% of eligible patients to consent to the main randomized study, with the vast majority of the MyLink-assigned group becoming engaged and completing follow-up. Achieving this requires identifying patients in real-time at the ED, frequent communications between researchers and CSWs, cultivating rapport during patient referral, enrollment, and follow-up, coordinating with other care management programs serving our patients, and adhering to MEP protocols that are rapidly evolving to address and overcome barriers. Challenges include: increasingly heavy CSW case-loads that decrease “warm” handoffs during the ED visit; problematic patient contact information; and incomplete program and follow-up assessments due to patient withdrawal, relocation, or death. These challenges lead to missing quality-of-life and healthcare utilization data needed for program evaluation. To reduce incomplete assessments, we lengthened time windows and expanded outreach methods (e.g., in-person upon ED revisit, web and medical record searches for updated contact information). We hypothesize that MyLink will improve patient quality-of-life and reduce ED utilization and total costs of care for super-utilizers

Health Evaluation and Referral Assistant: A Randomized Controlled Trial of a Web-Based Screening, Brief Intervention, and Referral to Treatment System to Reduce Risky Alcohol Use Among Emergency Department Patients

BACKGROUND: Computer technologies hold promise for implementing alcohol screening, brief intervention, and referral to treatment (SBIRT). Questions concerning the most effective and appropriate SBIRT model remain. OBJECTIVE: The aim of this study was to evaluate the impact of a computerized SBIRT system called the Health Evaluation and Referral Assistant (HERA) on risky alcohol use treatment initiation. METHODS: Alcohol users (N=319) presenting to an emergency department (ED) were considered for enrollment. Those enrolled (n=212) were randomly assigned to the HERA, to complete a patient-administered assessment using a tablet computer, or a minimal-treatment control, and were followed for 3 months. Analyses compared alcohol treatment provider contact, treatment initiation, treatment completion, and alcohol use across condition using univariate comparisons, generalized estimating equations (GEEs), and post hoc chi-square analyses. RESULTS: HERA participants (n=212; control=115; intervention=97) did not differ between conditions on initial contact with an alcohol treatment provider, treatment initiation, treatment completion, or change in risky alcohol use behavior. Subanalyses indicated that HERA participants, who accepted a faxed referral, were more likely to initiate contact with a treatment provider and initiate treatment for risky alcohol use, but were not more likely to continue engaging in treatment, or to complete treatment and change risky alcohol use behavior over the 3-month period following the ED visit. CONCLUSIONS: The HERA promoted initial contact with an alcohol treatment provider and initiation of treatment for those who accepted the faxed referral, but it did not lead to reduced risky alcohol use behavior. Factors which may have limited the HERA\u27s impact include lack of support for the intervention by clinical staff, the low intensity of the brief and stand-alone design of the intervention, and barriers related to patient follow-through, (eg, a lack of transportation or childcare, fees for services, or schedule conflicts). TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): NCT01153373; https://clinicaltrials.gov/ct2/show/NCT01153373 (Archived by WebCite at http://www.webcitation.org/6pHQEpuIF)

A Supersymmetric SO(10) Model with Inflation and Cosmic Strings

We have built a supersymmetric SO(10) model consistent with cosmological observations. The model gives rise to a false vacuum hybrid inflationary scenario which solves the monopole problem. We argue that this type of inflationary scenario is generic in supersymmetric SO(10) model, and arises naturally from the theory. Neither any external field nor any external symmetry has to be added. It can just be a consequence of the theory. In our specific model, at the end of inflation, cosmic strings form. The properties of the strings are presented. The cosmic background radiation anisotropies induced by the inflationary perturbations and the cosmic strings are estimated. The model produces a stable lightest superparticle and a very light left-handed neutrino which may serve as the cold and hot dark matter. The properties of a mixed cosmic string-inflationary large scale structure formation scenario are discussed.Comment: 32 pages, uses RevTex. Misprint in a referenc

Low-dose M.tb infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates

Introduction: Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund’s Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied. Methods: We set out to evaluate antibody responses to a range of unrelated pathogens following infection with Mycobacterium tuberculosis (M.tb) and vaccination with BCG or a candidate TB vaccine, MTBVAC, in non-human primates. Results: We demonstrate a significant increase in the titer of antibodies against SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, tetanus toxoid, and respiratory syncytial virus antigens following low-dose aerosol infection with M.tb. The magnitude of some of these responses correlated with TB disease severity. However, vaccination with BCG administered by the intradermal, intravenous or aerosol routes, or intradermal delivery of MTBVAC, did not increase antibody responses against unrelated pathogens. Discussion: Our findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID

A Structural Study of the Cytoplasmic Chaperone Effect of 14-3-3 Proteins on Ataxin-1

Expansion of the polyglutamine tract in the N terminus of Ataxin-1 is the main cause of the neurodegenerative disease, spinocerebellar ataxia type 1 (SCA1). However, the C-terminal part of the protein - including its AXH domain and a phosphorylation on residue serine 776 - also plays a crucial role in disease development. This phosphorylation event is known to be crucial for the interaction of Ataxin-1 with the 14-3-3 adaptor proteins and has been shown to indirectly contribute to Ataxin-1 stability. Here we show that 14-3-3 also has a direct anti-aggregation or chaperone effect on Ataxin-1. Furthermore, we provide structural and biophysical information revealing how phosphorylated S776 in the intrinsically disordered C terminus of Ataxin-1 mediates the cytoplasmic interaction with 14-3-3 proteins. Based on these findings, we propose that 14-3-3 exerts the observed chaperone effect by interfering with Ataxin-1 dimerization through its AXH domain, reducing further self-association. The chaperone effect is particularly important in the context of SCA1, as it was previously shown that a soluble form of mutant Ataxin-1 is the major driver of pathology