AT-121, ¿el opioide perfecto?

Los opioides son los analgésicos más potentes y efectivos de que disponemos en la actualidad. Su cara oscura la encarna el creciente aumento de pacientes adictos a su consumo en todo el mundo, principalmente en Estados Unidos. Desde el descubrimiento de los primeros opioides sintéticos, la industria farmacéutica se halla en busca de un analgésico que no genere tolerancia ni dependencia, ni efectos adversos respiratorios. La mayoría de los opiáceos son agonistas del receptor mu, cuya activación aumenta la disponibilidad sináptica de dopamina, neurotransmisor vehicular en circuitos de recompensa. Sin embargo, un cuarto receptor opioide ha sido descrito recientemente: el receptor de nociceptina/orfanina. Su activación inhibe la liberación de dopamina, evitando el refuerzo positivo que ocurre tras el consumo del fármaco. AT-121 es un agonista bifuncional MOP/NOP que ha sido probado en primates no humanos con resultados prometedores en cuanto a potencia analgésica, menores efectos secundarios sistémicos y menor tasa de adicción y abuso. Tales características hacen de esta molécula un arma esperanzadora en el tratamiento del dolor crónico o de la propia adicción a fármacos opioides. En los últimos años se han explorado distintos agonistas bifuncionales en roedores y primates no humanos con interesantes resultados; quedamos pues a la espera de futuras investigaciones en humanos. ABSTRACT Is AT121 the perfect opioid? Opioids are the most powerful and effective analgesics available today. Their dark side is reflected in the growing number of patients addicted to their use around the world, mainly in the United States. Since the discovery of the first synthetic opioids, the pharmaceutical industry has been searching for an analgesic that does not generate tolerance or dependence, nor adverse respiratory effects. Most opioids are mu receptor agonists, whose activation increases the synaptic availability of dopamine, a neurotransmitter that is a carrier in reward circuits. However, a fourth opioid receptor has recently been described: the nociceptin/orphanine receptor. Its activation inhibits the release of dopamine, preventing the positive reinforcement that occurs after drug consumption. AT-121 is a bifunctional MOP/NOP agonist that has been tested in non-human primates with promising results in terms of analgesic potency, fewer systemic side effects, and lower rate of addiction and abuse. Such characteristics make this molecule a hopeful weapon in the treatment of chronic pain or addiction to opioid drugs. In recent years, different bifunctional agonists have been explored in rodents and non-human primates with interesting results; we are therefore awaiting future research in humans.

Download Full-text

Fetal Outcomes with Detoxification from Opioid Drugs during Pregnancy: A Systematic Review

American Journal of Perinatology ◽

10.1055/s-0039-1688908 ◽

2019 ◽

Vol 37 (07) ◽

pp. 679-688 ◽

Cited By ~ 1

Author(s):

Craig V. Towers ◽

Paul Terry ◽

Breanne Rackley ◽

Mark Hennessy ◽

Kevin Visconti

Keyword(s):

Systematic Review ◽

Pregnancy Outcome ◽

Study Design ◽

Future Research ◽

Fetal Outcomes ◽

Term Newborn ◽

Number Of Patients ◽

Increased Risk ◽

Opioid Drugs

Objective This study aimed to perform a systematic review of all studies reporting fetal outcomes following detoxification or tapering of opioid drugs during pregnancy. Study Design PubMed, Scopus, Medline, and Google Scholar were searched, and only manuscripts clearly reporting pregnancy/fetal outcomes involving tapering or detoxification from opioid drugs were included. Only pregnancies managed after 1980 were included (when antenatal fetal surveillance became more routine). Collected data included study design, location, years patients were managed, number of patients who were tapered or detoxified, method of tapering, and pregnancy outcome. Results A total of 14 publications met the criteria for review after evaluating more than 2,000 abstracts and 153 published manuscripts. In 1,097 pregnancies, based on mortality rate analyses and forest plots, no increased fetal risks due to tapering or detoxification from opioid drugs were identified. No increased risk of preterm delivery was found. Conclusion Pregnant women with opioid use disorder who are stable in a medication-assisted treatment program with behavioral health can be informed that tapering or full detoxification from opioid drugs does not increase the fetal risk of poor pregnancy outcome. Future research needs to answer the questions on maternal and long-term newborn consequences of tapering or detoxification versus long-term newborn consequences of continued chronic in utero opioid exposure.

Download Full-text

Refining Evidence-Based Treatments for Late-Life Depression

GeroPsych ◽

10.1024/1662-9647/a000127 ◽

2015 ◽

Vol 28 (2) ◽

pp. 67-76

Author(s):

Grace C. Niu ◽

Patricia A. Arean

Keyword(s):

Older Adults ◽

Mental Illness ◽

Brain Plasticity ◽

Late Life ◽

Aging Population ◽

The United States ◽

Future Research ◽

Evidence Based ◽

Late Life Depression ◽

Evidence Based Treatments

The recent increase in the aging population, specifically in the United States, has raised concerns regarding treatment for mental illness among older adults. Late-life depression (LLD) is a complex condition that has become widespread among the aging population. Despite the availability of behavioral interventions and psychotherapies, few depressed older adults actually receive treatment. In this paper we review the research on refining treatments for LLD. We first identify evidence-based treatments (EBTs) for LLD and the problems associated with efficacy and dissemination, then review approaches to conceptualizing mental illness, specifically concepts related to brain plasticity and the Research Domain Criteria (RDoc). Finally, we introduce ENGAGE as a streamlined treatment for LLD and discuss implications for future research.

Download Full-text

A Silenced Population

Crisis ◽

10.1027/0227-5910/a000470 ◽

2017 ◽

Vol 38 (6) ◽

pp. 433-442 ◽

Cited By ~ 1

Author(s):

Kim Gryglewicz ◽

Melanie Bozzay ◽

Brittany Arthur-Jordon ◽

Gabriela D. Romero ◽

Melissa Witmeier ◽

...

Keyword(s):

At Risk ◽

Depressive Symptomatology ◽

The United States ◽

Future Research ◽

At Risk Youth ◽

Peer Relationship ◽

Student Records ◽

Cross Sectional ◽

Increased Risk ◽

Method Student

Abstract. Background: Given challenges that exceed the normal developmental requirements of adolescence, deaf and hard-of-hearing (DHH) youth are believed to be at elevated risk for engaging in suicide-related behavior (SRB). Unfortunately, little is known about the mechanisms that put these youth potentially at risk. Aims: To determine whether peer relationship difficulties are related to increased risk of SRB in DHH youth. Method: Student records (n = 74) were retrieved from an accredited educational center for deaf and blind students in the United States. Results: Peer relationship difficulties were found to be significantly associated with engagement in SRB but not when accounting for depressive symptomatology. Limitations: The restricted sample limits generalizability. Conclusions regarding risk causation cannot be made due to the cross-sectional nature of the study. Conclusion: These results suggest the need for future research that examines the mechanisms of the relationship between peer relationship difficulties, depression, and suicide risk in DHH youth and potential preventive interventions to ameliorate the risks for these at-risk youth.

Download Full-text

Electronic cigarettes: How confident and effective are allergists, pulmonologists, and primary care physicians in their practice behavior?

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200009 ◽

2020 ◽

Vol 41 (3) ◽

pp. 192-197

Author(s):

Sherry S. Zhou ◽

Alan P. Baptist

Keyword(s):

Primary Care ◽

Primary Care Physicians ◽

Electronic Cigarettes ◽

The United States ◽

Fisher Exact Test ◽

Exact Test ◽

Knowledge And Beliefs ◽

Tobacco Cigarette ◽

Number Of Patients ◽

Personal Use

Background: There has been a striking increase in electronic cigarette (EC) use in the United States. The beliefs and practices toward ECs among physicians are unknown. Objective: The purpose of this study was to investigate EC practice patterns among allergists, pulmonologists, and primary care physicians. Methods: An anonymous survey was sent to physicians. The survey contained 32 questions and addressed issues related to demographics, cessation counseling behaviors, personal use, and knowledge and beliefs about ECs. Statistical analysis was performed by using analysis of variance, the Pearson χ2 test, Fisher exact test, and logistic regression. Results: A total of 291 physicians completed the survey (222 primary care physicians, 33 pulmonologists, and 36 allergists) for a response rate of 46%. The allergists asked about tobacco cigarette use as frequently as did the pulmonologists and more than the primary care physicians (p < 0.001), but they rarely asked about EC use. The pulmonologists scored highest on self-reported knowledge on ECs, although all the groups answered <40% of the questions correctly. The allergists did not feel as comfortable about providing EC cessation counseling as did the pulmonologists and primary care physicians (p < 0.001). All three groups were equally unlikely to recommend ECs as a cessation tool for tobacco cigarette users. Conclusion: Allergists lacked knowledge and confidence in providing education and cessation counseling for EC users. As the number of patients who use these products continues to increase, there is an urgent need for all physicians to be comfortable and knowledgeable with counseling about ECs.

Download Full-text

Mosquito and Tick-borne Illnesses in the United States. Guidelines for the Recognition and Empiric Treatment of Zoonotic Diseases in the Wilderness.

Infectious Disorders - Drug Targets ◽

10.2174/1871526518666180626123340 ◽

2019 ◽

Vol 19 (3) ◽

pp. 238-257

Author(s):

Suresh Antony

Keyword(s):

United States ◽

Lyme Disease ◽

Spotted Fever ◽

Disease Process ◽

Rocky Mountain ◽

The United States ◽

Health Care Facilities ◽

Diagnostic Tools ◽

Rocky Mountain Spotted Fever ◽

Number Of Patients

Background:In the United States, tick-borne illnesses account for a significant number of patients that have been seen and treated by health care facilities. This in turn, has resulted in a significant morbidity and mortality and economic costs to the country.Methods:The distribution of these illnesses is geographically variable and is related to the climate as well. Many of these illnesses can be diagnosed and treated successfully, if recognized and started on appropriate antimicrobial therapy early in the disease process. Patient with illnesses such as Lyme disease, Wet Nile illness can result in chronic debilitating diseases if not recognized early and treated.Conclusion:This paper covers illnesses such as Lyme disease, West Nile illness, Rocky Mountain Spotted fever, Ehrlichia, Tularemia, typhus, mosquito borne illnesses such as enteroviruses, arboviruses as well as arthropod and rodent borne virus infections as well. It covers the epidemiology, clinical features and diagnostic tools needed to make the diagnosis and treat these patients as well.

Download Full-text

"Taming the Monster aka Uncontrolled Diabetes: A Viewpoint" (Preprint)

10.2196/preprints.25150 ◽

2020 ◽

Author(s):

Swati Anand ◽

Amardeep Kalsi ◽

Jonathan Figueroa ◽

Parag Mehta

Keyword(s):

Blood Glucose ◽

Diabetes Management ◽

Positive Impact ◽

The United States ◽

Phone Call ◽

Diabetic Patients ◽

Dietary Compliance ◽

Glucose Levels ◽

Uncontrolled Diabetes ◽

Number Of Patients

BACKGROUND HbA1c between 6% and 6.9% is associated with the lowest incidence of all‐cause and CVD mortality, with a stepwise increase in all‐cause and cardiovascular mortality in those with an HbA1c >7%. • There are 30 million individuals in the United States (9.4% of the population) currently living with Diabetes Mellitus. OBJECTIVE Improving HbA1C levels in patients with uncontrolled Diabetes with a focused and collaborative effort. METHODS Our baseline data for Diabetic patients attending the outpatient department from July 2018 to July 2019 in a University-affiliated hospital showed a total of 217 patients for one physician. • Of 217 patients, 17 had HbA1C 9 and above. We contacted these patients and discussed the need for tight control of their blood glucose levels. We intended to ensure them that we care and encourage them to participate in our efforts to improve their outcome. • We referred 13 patients that agreed to participate to the Diabetic educator who would schedule an appointment with the patients, discuss their diet, exercise, how to take medications, self-monitoring, and psychosocial factors. • If needed, she would refer them to the Nutritionist based on patients’ dietary compliance. • The patients were followed up in the next two weeks via telemedicine or a phone call by the PCP to confirm and reinforce the education provided by the diabetes educator. RESULTS Number of patients that showed an improvement in HbA1C values: 11 Cumulative decrease in HbA1C values for 13 patients: 25.3 The average reduction in HbA1C: 1.94 CONCLUSIONS Our initiative to exclusively target the blood glucose level with our multidisciplinary approach has made a positive impact, which is reflected in the outcome. • It leads to an improvement in patient compliance and facilitates diabetes management to reduce the risk for complications CLINICALTRIAL NA

Download Full-text

The Development of an Online Tobacco Tracker Tool to Crowdsource Campus Environmental Reports for Smoke and Tobacco Free College Policies: A Mixed Methods Study (Preprint)

10.2196/preprints.26280 ◽

2020 ◽

Author(s):

Sabrina F. Loureiro ◽

Kim M. Pulvers ◽

Melissa M. Gosdin ◽

Keavagh R. Clift ◽

Myra J. Rice ◽

...

Keyword(s):

Mixed Methods ◽

Focus Groups ◽

Positive Reinforcement ◽

The United States ◽

College Campuses ◽

Policy Enforcement ◽

Sequential Mixed Methods ◽

Effective Policy ◽

Online Tracking ◽

One Year

BACKGROUND College campuses in the United States have begun implementing Smoke and Tobacco-Free policies to discourage the use of tobacco. Smoke and Tobacco-Free policies, however, are contingent upon effective policy enforcement. OBJECTIVE To develop an empirically-derived online tracking tool (Tracker) for crowdsourcing campus environmental reports of tobacco use and waste to support smoke and tobacco-free college policies. METHODS An exploratory sequential mixed methods approach was utilized to inform the development and evaluation of the Tracker. In October 2018, three focus groups across two California universities were conducted and themes were analyzed, guiding Tracker development. After one year of implementation, users were asked in April 2020 to complete a survey about their experience. RESULTS In the focus groups, two major themes emerged: barriers and facilitators to tool utilization. Further Tracker development was guided by focus group input to address these barriers (e.g. information, policing, and logistical concerns) and facilitators (e.g. environmental motivators, positive reinforcement). Amongst 1,163 Tracker reports, those who completed the user survey (n=316) reported the top motivations to using the tool were having a cleaner environment (79%) and health concerns (69%). CONCLUSIONS Environmental concerns, a motivator which emerged in focus groups, shaped the Tracker’s development and was cited by the majority of users surveyed as a top motivator for utilization.

Download Full-text

Fragments of the American Dream: Immigration, Race, and Medical Care in the Segregated South, 1929

Public Voices ◽

10.22140/pv.111 ◽

2016 ◽

Vol 13 (2) ◽

pp. 1

Author(s):

John R Phillips

Keyword(s):

United States ◽

American Dream ◽

Black Population ◽

The United States ◽

Single Woman ◽

Future Research ◽

Legal Doctrine ◽

Quarter Century ◽

History Of ◽

Sunflower County

The cover photograph for this issue of Public Voices was taken sometime in the summer of 1929 (probably June) somewhere in Sunflower County, Mississippi. Very probably the photo was taken in Indianola but, perhaps, it was Ruleville. It is one of three such photos, one of which does have the annotation on the reverse “Ruleville Midwives Club 1929.” The young woman wearing a tie in this and in one of the other photos was Ann Reid Brown, R.N., then a single woman having only arrived in the United States from Scotland a few years before, in 1923. Full disclosure: This commentary on the photo combines professional research interests in public administration and public policy with personal interests—family interests—for that young nurse later married and became the author’s mother. From the scholarly perspective, such photographs have been seen as “instrumental in establishing midwives’ credentials and cultural identity at a key transitional moment in the history of the midwife and of public health” (Keith, Brennan, & Reynolds 2012). There is also deep irony if we see these photographs as being a fragment of the American dream, of a recent immigrant’s hope for and success at achieving that dream; but that fragment of the vision is understood quite differently when we see that she began a hopeful career working with a Black population forcibly segregated by law under the incongruously named “separate but equal” legal doctrine. That doctrine, derived from the United States Supreme Court’s 1896 decision, Plessy v. Ferguson, would remain the foundation for legally enforced segregation throughout the South for another quarter century. The options open to the young, white, immigrant nurse were almost entirely closed off for the population with which she then worked. The remaining parts of this overview are meant to provide the following: (1) some biographical information on the nurse; (2) a description, in so far as we know it, of why she was in Mississippi; and (3) some indication of areas for future research on this and related topics.

Download Full-text

Questions

10.1093/oso/9780190865214.003.0007 ◽

2018 ◽

Cited By ~ 1

Author(s):

James L. Gibson ◽

Michael J. Nelson

Keyword(s):

United States ◽

African Americans ◽

Supreme Court ◽

Legal System ◽

Public Support ◽

The United States ◽

Future Research ◽

White Americans ◽

Two Factors ◽

The U.S

We have investigated the differences in support for the U.S. Supreme Court among black, Hispanic, and white Americans, catalogued the variation in African Americans’ group attachments and experiences with legal authorities, and examined how those latter two factors shape individuals’ support for the U.S. Supreme Court, that Court’s decisions, and for their local legal system. We take this opportunity to weave our findings together, taking stock of what we have learned from our analyses and what seem like fruitful paths for future research. In the process, we revisit Positivity Theory. We present a modified version of the theory that we hope will guide future inquiry on public support for courts, both in the United States and abroad.

Download Full-text

Introduction

10.1093/oxfordhb/9780190248178.013.1 ◽

2017 ◽

Author(s):

Travis D. Stimeling

Keyword(s):

United States ◽

The United States ◽

Country Music ◽

Future Research ◽

Music Culture ◽

Rich Variety ◽

Ethnographic Studies ◽

Folklore Studies ◽

History Of ◽

The Rich

This chapter offers a historiographic survey of country music scholarship from the publication of Bill C. Malone’s “A History of Commercial Country Music in the United States, 1920–1964” (1965) to the leading publications of the today. Very little of substance has been written on country music recorded since the 1970s, especially when compared to the wealth of available literature on early country recording artists. Ethnographic studies of country music and country music culture are rare, and including ethnographic methods in country music studies offers new insights into the rich variety of ways in which people make, consume, and engage with country music as a genre. The chapter traces the influence of folklore studies, sociology, cultural studies, and musicology on the development of country music studies and proposes some directions for future research in the field.

Download Full-text