A qualitative exploration of the use of telehealth for opioid treatment: Implications for nurse-managed care.

AIM: To characterise experiences with telehealth for Medications for Opioid Use Disorder (MOUD) services among patients, prescribers, nurses and substance use counsellors to inform future best practices. DESIGN: We engaged a qualitative descriptive study design. METHODS: Semi-structured interviews were conducted with prescribers (nurse practitioners and physicians, n = 20), nurses and substance use counsellors (n = 7), and patients (n = 20) between June and September 2021. Interviews were verbatim transcribed. Thematic analysis was conducted using a qualitative descriptive method. RESULTS: Among both providers and patients, four themes were identified: (1) Difficulties with telehealth connection (2) Flexibility in follow-up and retention, (3) Policy changes that enabled expanded care, (4) Path forward with telehealth. Two additional findings emerged from provider interviews: (1) Expansion of nurse-managed office-based opioid treatment, and (2) Novel methods to engage patients. CONCLUSIONS: Patients and providers continued to view telehealth as an acceptable means for delivery and management of MOUD, particularly when utilised in a hybrid manner between in-person visits. Nurse-managed care for this service was evident as nurses extended the breadth of services offered and utilised novel methods such as text messages and management of 'call-in' lines to engage patients. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Use of telehealth for MOUD should be incorporated into practice settings to reach patients in a flexible manner. Nurses in particular can use this medium to extend office-based opioid treatment by conducting assessments and expanding capacity for other wrap-around services. IMPACT: We identify recommendations for best practices in the use of telehealth for opioid use disorder management and highlight the value of nurse-managed care. REPORTING METHOD: The consolidated criteria for reporting qualitative research. PATIENT OR PUBLIC CONTRIBUTION: Patients with opioid use disorder and prescribers with experience using telehealth were interviewed for this study.

Barriers to Assessing and Treating Trauma in Primary Care and Opportunities for Improvement: Perspectives from Prescribers of Medications for Opioid Use Disorder.

Background: Medication for Opioid Use Disorder (MOUD) is a best practice for treating individuals with opioid use disorder (OUD), and primary care-based MOUD management can reduce treatment barriers among OUD patients. Individuals with OUD experience disproportionately high rates of trauma and violence, highlighting the importance of addressing trauma, mental health, and substance use concurrently. However, clear guidelines for trauma-informed treatment in a primary care setting remain poorly established. Methods: A qualitative approach was engaged to explore primary care providers' perceptions of barriers and facilitators to assessing and treating trauma among MOUD patients. Twenty in-depth interviews were conducted in 2021 with Baltimore-based MOUD prescribers, including primary care physicians and nurse practitioners. Interview questions assessed experiences with identifying and treating trauma among MOUD patients, including challenges and opportunities. Results: Providers reported extensive histories of trauma experienced by MOUD patients. Barriers to addressing trauma include a lack of standardized protocols/procedures for identifying trauma, insufficient training/time to assess and treat trauma, and the limited availability of external mental health providers and specialty services. Opportunities included building strong, mutually respectful patient-provider relationships, providing individualized, person-centered care, and establishing connections to coordinated multidisciplinary treatment networks. Conclusions: MOUD treatment within primary care is an important way to increase OUD treatment access, but clearer standards are needed for the treatment of trauma within this patient population. These findings demonstrate opportunities to improve standards and systems such that primary care providers are better equipped to assess and treat the complex histories of trauma experienced by individuals with OUD.

Peer Approaches to Improve HIV Care Cascade Outcomes: a Scoping Review Focused on Peer Behavioral Mechanisms.

PURPOSE OF REVIEW: There are three main components of peer-based approaches regardless of type: education, social support, and social norms. The purpose of this scoping review was to examine evidence in the literature among peer-based interventions and programs of components and behavioral mechanisms utilized to improve HIV care cascade outcomes. RECENT FINDINGS: Of 522 articles found, 40 studies were included for data abstraction. The study outcomes represented the entire HIV care cascade from HIV testing to viral suppression. Most were patient navigator models and 8 of the studies included all three components. Social support was the most prevalent component. Role modeling of behaviors was less commonly described. This review highlighted the peer behavioral mechanisms that operate in various types of peer approaches to improve HIV care and outcomes in numerous settings and among diverse populations. The peer-based approach is flexible and commonly used, particularly in resource-poor settings.

Psychosocial Interventions to Promote Undetectable HIV Viral Loads: A Systematic Review of Randomized Clinical Trials.

Suppressing HIV viral loads to undetectable levels is essential for ending the HIV/AIDS epidemic. We evaluated randomized controlled trials aimed to increase antiretroviral medication adherence and promote undetectable viral loads among people living with HIV through November 22, 2019. We extracted data from 51 eligible interventions and analyzed the results using random effects models to compare intervention effects between groups within each intervention and across interventions. We also evaluated the relation between publication date and treatment effects. Only five interventions increased undetectable viral loads significantly. As a whole, the analyzed interventions were superior to Standard of Care in promoting undetectable viral loads. Interventions published more recently were not more effective in promoting undetectable viral loads. No treatment category consistently produced significant increases in undetectable viral loads. To end the HIV/AIDS epidemic, we should use interventions that can suppress HIV viral loads to undetectable levels.

Social Network Influence on Syphilis Testing for Black Sexual Minority Men in Baltimore, Maryland: A Cross-sectional Social Network Analysis.

ABSTRACT: Black sexual minority men (BSMM), including those with HIV, have disproportionate rates of syphilis infection. This study examines the associations of social network characteristics on syphilis testing, given that social network approaches are well established as effective methods to establish health-promoting social norms. We analyzed baseline data from a sexual health behavioral intervention. Using multivariable logistic regression, we modeled individual and social network characteristics on syphilis testing. Of the 256 participants, 37% tested for syphilis in the past year. In the adjusted model controlling for individual factors, odds of syphilis testing increased 89% for each increase in network member participants being encouraged to get a syphilis test (95% confidence interval [1.19-3.00]). Feeling comfortable accompanying a friend for HIV/sexually transmitted infection testing was associated with 2.47 increased odds of syphilis testing. Encouraging and training individuals to discuss sexual health topics with their network members may lead to the establishment of testing in social networks of Black sexual minority men.

Metabolism of soluble sugars in developing melon fruit: a global transcriptional view of the metabolic transition to sucrose accumulation.

The sweet melon fruit is characterized by a metabolic transition during its development that leads to extensive accumulation of the disaccharide sucrose in the mature fruit. While the biochemistry of the sugar metabolism pathway of the cucurbits has been well studied, a comprehensive analysis of the pathway at the transcriptional level allows for a global genomic view of sugar metabolism during fruit sink development. We identified 42 genes encoding the enzymatic reactions of the sugar metabolism pathway in melon. The expression pattern of the 42 genes during fruit development of the sweet melon cv Dulce was determined from a deep sequencing analysis performed by 454 pyrosequencing technology, comprising over 350,000 transcripts from four stages of developing melon fruit flesh, allowing for digital expression of the complete metabolic pathway. The results shed light on the transcriptional control of sugar metabolism in the developing sweet melon fruit, particularly the metabolic transition to sucrose accumulation, and point to a concerted metabolic transition that occurs during fruit development.

Effects of incentivizing viral suppression in previously incarcerated adults living with HIV.

Background: The amount of HIV in a person's blood can be suppressed to an undetectable level through antiretroviral therapy medications (ART). Adhering to an ART regimen can improve a person's health and reduce HIV transmission. Despite these benefits, many people with HIV do not maintain the level of adherence required to achieve an undetectable viral load. This problem is particularly common among people who have been incarcerated.Objective: To determine effects of incentivizing viral suppression in previously incarcerated adults with HIV.Methods: Adults with HIV (N = 102) and detectable viral load (>200 copies/mL) were randomly assigned to a Usual Care or Incentive group. Usual Care participants did not earn incentives for viral suppression. Incentive participants earned incentives ($10/day maximum) for providing blood samples with a reduced or undetectable (<200 copies/mL) viral load. Assessments were conducted every 3 months. Results collected during the first year were aggregated and compared based on group assignment and incarceration history.Results: Previously incarcerated participants in the Incentive group provided more (OR: 2.9; CI: 1.3-6.8; p <.05) blood samples with an undetectable viral load (69%) than those in the Usual Care group (41%). Never-incarcerated participants in the Incentive group provided more (OR: 6.8; CI: 2.2-21.0; p <.01) blood samples with an undetectable viral load (78%) than those in the Usual Care group (36%). Effects of incentives did not differ by incarceration history.Conclusions: Incentivizing viral suppression can increase viral suppression (undetectable viral load) in people who have been incarcerated.

Effects of incentives on viral suppression in people living with HIV who use cocaine or opiates.

BACKGROUND: Antiretroviral therapy (ART) adherence is essential to maintenance of undetectable viral loads among people living with HIV, which improves health and reduces HIV transmission. Despite these benefits, some people living with HIV do not maintain the level of adherence required to sustain an undetectable viral load. This problem is particularly common among people who use drugs. OBJECTIVE: To determine effects of incentivizing viral suppression in people living with HIV who used cocaine or opiates. METHODS: In this secondary analysis of data collected during a randomized controlled trial, participants (N=102) with detectable HIV viral loads (>200 copies/mL) were randomly assigned to a Usual Care or Incentive group. Usual Care participants did not earn incentives for viral suppression. Incentive participants earned incentives ($10/day maximum) for providing blood samples with reduced or undetectable (<200 copies/mL) viral loads. All participants completed assessments every three months. Results collected during the first year were compared based on group assignment and drug use. RESULTS: Among participants who used cocaine or opiates, Incentive participants (n = 27) provided more (OR:4.0, CI:1.6-10.3, p = .004) blood samples with an undetectable viral load (69 %) than Usual Care participants (n = 25; 41 %). Among participants who did not use cocaine or opiates, Incentive participants (n = 25) provided more (OR:4.1, CI:1.5-10.7, p = .005) blood samples with an undetectable viral load (78 %) than Usual Care participants (n = 25; 36 %). Effects of incentives did not differ by drug use (OR:1.0, CI:0.3-4.0, p = .992). CONCLUSIONS: Incentivizing viral suppression can promote undetectable viral loads in people living with HIV who use cocaine or opiates.

RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation.

Healthy mitochondria use an electrochemical gradient across the inner mitochondrial membrane (IMM) to generate energy in the form of ATP. A variety of endogenous and exogenous factors can lead to transient or sustained depolarization of the IMM, including mitochondrial fission events, expression of uncoupling proteins, electron transport chain (ETC) inhibitors, or chemical uncouplers. This depolarization in turn leads to a variety of physiological responses, ranging from selective mitochondrial clearance (mitophagy) to cell death. How cells recognize and ultimately respond to depolarized mitochondria remains incompletely understood. Here we show that the small GTPases RalA and RalB both relocalize to mitochondria following depolarization in a process dependent on clathrin-mediated endocytosis (CME). Furthermore, both genetic and pharmacologic inhibition of RalA and RalB leads to an increase in the activity of the atypical IκB kinase TBK1 both basally and in response to mitochondrial depolarization. This phenotype was also observed following inhibition of Ral relocalization. Collectively, these data suggest a model in which RalA and RalB inhibit TBK1 and that relocalization of Ral to depolarized mitochondria facilitates TBK1 activation through release of this inhibition.

Drp1 Promotes KRas-Driven Metabolic Changes to Drive Pancreatic Tumor Growth.

Mitochondria undergo fission and fusion to maintain homeostasis, and tumors exhibit the dysregulation of mitochondrial dynamics. We recently demonstrated that ectopic HRasG12V promotes mitochondrial fragmentation and tumor growth through Erk phosphorylation of the mitochondrial fission GTPase Dynamin-related protein 1 (Drp1). However, the role of Drp1 in the setting of endogenous oncogenic KRas remains unknown. Here, we show that Drp1 is required for KRas-driven anchorage-independent growth in fibroblasts and patient-derived pancreatic cancer cell lines, and it promotes glycolytic flux, in part through the regulation of hexokinase 2 (HK2). Furthermore, Drp1 deletion imparts a significant survival advantage in a model of KRas-driven pancreatic cancer, and tumors exhibit a strong selective pressure against complete Drp1 deletion. Rare tumors that arise in the absence of Drp1 have restored glycolysis but exhibit defective mitochondrial metabolism. This work demonstrates that Drp1 plays dual roles in KRas-driven tumor growth: supporting both glycolysis and mitochondrial function through independent mechanisms.

Systematic identification of abundant A-to-I editing sites in the human transcriptome.

RNA editing by members of the ADAR (adenosine deaminases acting on RNA) family leads to site-specific conversion of adenosine to inosine (A-to-I) in precursor messenger RNAs. Editing by ADARs is believed to occur in all metazoa, and is essential for mammalian development. Currently, only a limited number of human ADAR substrates are known, whereas indirect evidence suggests a substantial fraction of all pre-mRNAs being affected. Here we describe a computational search for ADAR editing sites in the human transcriptome, using millions of available expressed sequences. We mapped 12,723 A-to-I editing sites in 1,637 different genes, with an estimated accuracy of 95%, raising the number of known editing sites by two orders of magnitude. We experimentally validated our method by verifying the occurrence of editing in 26 novel substrates. A-to-I editing in humans primarily occurs in noncoding regions of the RNA, typically in Alu repeats. Analysis of the large set of editing sites indicates the role of editing in controlling dsRNA stability.

Grey matter abnormalities in first-episode schizophrenia and affective psychosis.

BACKGROUND: Grey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosis. AIMS: To determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosis. METHOD: We obtained dual-echo (proton density/T2-weighted) magnetic resonance images and carried out voxel-based analysis on the images of 73 patients with first-episode psychosis (schizophrenia n=44, affective psychosis n=29) and 58 healthy controls. RESULTS: Both patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical threshold. CONCLUSIONS: Both schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas.

A musculoskeletal model of the equine forelimb for determining surface stresses and strains in the humerus--part I. Mathematical modeling.

Knowledge of the forces that act upon the equine humerus while the horse is standing and the resulting strains experienced by the bone is useful for the prevention and treatment of fractures and for assessing the proximolateral aspect of the bone as a site for obtaining autogenous bone graft material. The first objective was to develop a mathematical model to predict the loads on the proximal half of the humerus created by the surrounding musculature and ground reaction forces while the horse is standing. The second objective was to calculate surface bone stresses and strains at three cross sections on the humerus corresponding to the donor site for bone grafts, a site predisposed to stress fracture, and the middle of the diaphysis. A three-dimensional mathematical model employing optimization techniques and asymmetrical beam analysis was used to calculate shoulder muscle forces and surface strains on the proximal and mid-diaphyseal aspects of the humerus. The active shoulder muscles, which included the supraspinatus, infraspinatus, subscapularis, and short head of the deltoid, produced small forces while the horse is standing; all of which were limited to 4.3% of their corresponding maximum voluntary contraction. As a result, the strains calculated at the proximal cross sections of the humerus were small, with maximum compressive strains of -104microepsilon at the cranial aspect of the bone graft donor cross section. The middle of the diaphysis experienced larger strain magnitudes with compressive strains at the lateral and the caudal aspects and tensile strains at the medial and cranial aspects (-377microepsilon and 258microepsilon maximum values, respectively) while the horse is standing. Small strains at the donor bone graft site do not rule out using this location to harvest bone graft tissue, although strains while rising to a standing position during recovery from anesthesia are unknown. At the site common to stress fractures, small strains imply that the stresses seen by this region while the horse is standing, although applied for long periods of time, are not a cause of fracture in this location. Knowing the specific regions of the middle of the diaphysis of the humerus that experience tensile and compressive strains is valuable in determining optimum placement of internal fixation devices for the treatment of complete fractures.

A musculoskeletal model of the equine forelimb for determining surface stresses and strains in the humerus-part II. Experimental testing and model validation.

The first objective of this study was to experimentally determine surface bone strain magnitudes and directions at the donor site for bone grafts, the site predisposed to stress fracture, the medial and cranial aspects of the transverse cross section corresponding to the stress fracture site, and the middle of the diaphysis of the humerus of a simplified in vitro laboratory preparation. The second objective was to determine whether computing strains solely in the direction of the longitudinal axis of the humerus in the mathematical model was inherently limited by comparing the strains measured along the longitudinal axis of the bone to the principal strain magnitudes and directions. The final objective was to determine whether the mathematical model formulated in Part I [Pollock et al., 2008, ASME J. Biomech. Eng., 130, p. 041006] is valid for determining the bone surface strains at the various locations on the humerus where experimentally measured longitudinal strains are comparable to principal strains. Triple rosette strain gauges were applied at four locations circumferentially on each of two cross sections of interest using a simplified in vitro laboratory preparation. The muscles included the biceps brachii muscle in addition to loaded shoulder muscles that were predicted active by the mathematical model. Strains from the middle grid of each rosette, aligned along the longitudinal axis of the humerus, were compared with calculated principal strain magnitudes and directions. The results indicated that calculating strains solely in the direction of the longitudinal axis is appropriate at six of eight locations. At the cranial and medial aspects of the middle of the diaphysis, the average minimum principal strain was not comparable to the average experimental longitudinal strain. Further analysis at the remaining six locations indicated that the mathematical model formulated in Part I predicts strains within +/-2 standard deviations of experimental strains at four of these locations and predicts negligible strains at the remaining two locations, which is consistent with experimental strains. Experimentally determined longitudinal strains at the middle of the diaphysis of the humerus indicate that tensile strains occur at the cranial aspect and compressive strains occur at the caudal aspect while the horse is standing, which is useful for fracture fixation.

Bridging expressed sequence alignments through targeted cDNA sequencing.

One of the major challenges in genome research is the identification of the complete set of genes in a genome. Alignments of expressed sequences (RNA and EST) with genomic sequences have been used to characterize genes. However, the number of alignments far exceeds the likely number of genes in a genome, suggesting that, for many genes, two or more alignments can be joined through overlapping sequences to yield accurate gene structures. High-throughput EST sequencing becomes less efficient in closing those alignment gaps due to its nonselective nature. We sought to bridge these alignments through a novel approach: targeted cDNA sequencing. Human expressed sequences from GenBank version 124 were aligned with the genomic sequence from NCBI build 24 using LEADS, Compugen's EST and RNA clustering and assembly software system. Nine hundred forty-eight pairs of alignments were selected based on EST clone information and/or their homology to the same known proteins. Reverse transcriptase PCR and sequencing yielded sequences for 363 of those pairs. These sequences helped characterize over 60 novel or otherwise incomplete genes in the recent UniGene build 153, which included over 1 million additional ESTs. These results indicate that this integrated and targeted strategy, combining computational prediction and experimental cDNA sequencing, can efficiently generate the overlapping sequences and enable the full characterization of genomes. Additional information about the contig pairs, the resultant overlapping sequences, tissue sources, and tissue profiles are available in a supplemental file.