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1.
J Addict Med ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829042

RESUMO

BACKGROUND: High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. METHODS: A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. RESULTS: A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. CONCLUSIONS: Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.

2.
Drug Alcohol Depend ; 259: 111274, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38643529

RESUMO

BACKGROUND: Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS: This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS: MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION: MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.


Assuntos
Buprenorfina , Prisões Locais , Metadona , Overdose de Opiáceos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Prisioneiros , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Overdose de Opiáceos/tratamento farmacológico , Buprenorfina/uso terapêutico , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Estudos de Coortes , Serviço Hospitalar de Emergência , Adulto Jovem , Encarceramento
3.
Addiction ; 119(7): 1313-1321, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38519819

RESUMO

Medications for opioid use disorder (MOUD) increase retention in care and decrease mortality during active treatment; however, information about the comparative effectiveness of different forms of MOUD is sparse. Observational comparative effectiveness studies are subject to many types of bias; a robust framework to minimize bias would improve the quality of comparative effectiveness evidence. This paper discusses the use of target trial emulation as a framework to conduct comparative effectiveness studies of MOUD with administrative data. Using examples from our planned research project comparing buprenorphine-naloxone and extended-release naltrexone with respect to the rates of MOUD discontinuation, we provide a primer on the challenges and approaches to employing target trial emulation in the study of MOUD.


Assuntos
Combinação Buprenorfina e Naloxona , Pesquisa Comparativa da Efetividade , Naltrexona , Antagonistas de Entorpecentes , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Antagonistas de Entorpecentes/uso terapêutico , Combinação Buprenorfina e Naloxona/uso terapêutico , Naltrexona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Buprenorfina/uso terapêutico , Estudos Observacionais como Assunto , Preparações de Ação Retardada , Projetos de Pesquisa , Naloxona/uso terapêutico
4.
Neurohospitalist ; 14(1): 104-105, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235032

RESUMO

We present a case and video of a 31-year-old man with biopsy-confirmed tumefactive demyelination affecting the right internal capsule causing left hemiplegia, excessive yawning, and the curious but well-described phenomenon of parakinesia brachialis oscitans (PBO) with transient tonic elevation of his paralyzed arm while yawning. PBO is most commonly reported in ischemic stroke with internal capsule or pontomedullary brainstem lesions. Our case uniquely demonstrates this phenomenon in the case of tumefactive demyelination. We also highlight excessive yawning which has also been described in multiple sclerosis.

5.
J Subst Use Addict Treat ; 158: 209254, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38072387

RESUMO

BACKGROUND: Treatment with methadone and buprenorphine medications for opioid use disorder (MOUD) during incarceration may lead to better community re-entry, but evidence on these relationships have been mixed. We aimed to identify community re-entry patterns and examine the association between in-jail MOUD and a pattern of successful reentry defined by rare occurrence of reincarceration and preventable healthcare utilization. METHODS: Data came from a retrospective, observational cohort study of 6066 adults with opioid use disorder who were incarcerated in New York City jails and released to the community during 2011-14. An outcome was community re-entry patterns identified by sequence analysis of 3-year post-release reincarceration, emergency department visits, and hospitalizations. An exposure was receipt of in-jail MOUD versus out-of-treatment (42 % vs. 58 %) for the last 3 days before discharge. The study accounted for differences in baseline demographic, clinical, behavioral, housing, and criminal legal characteristics between in-jail MOUD and out-of-treatment groups via propensity score matching. RESULTS: This study identified five re-entry patterns: stability (64 %), hospitalization (23 %), delayed reincarceration (7 %), immediate reincarceration (4 %), and continuous incarceration (2 %). After addressing confounding, 64 % and 57 % followed the stability pattern among MOUD and out-of-treatment groups who were released from jail in 2011, respectively. In 2012-14, the prevalence of following the stability pattern increased year-by-year while a consistently higher prevalence was observed among those with in-jail MOUD. CONCLUSIONS: Sequence analysis helped define post-release stability based on health and criminal legal system involvement. Receipt of in-jail MOUD was associated with a marker of successful community re-entry.


Assuntos
Prisões Locais , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Metadona/uso terapêutico , Análise de Sequência
6.
J Addict Med ; 17(5): 517-520, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37788602

RESUMO

INTRODUCTION: Recent findings support the provision of meditation-based interventions (MBIs) in primary care. However, the acceptability of MBI among patients prescribed medications for opioid use disorder (eg, buprenorphine) in primary care remains unclear. This study assessed experiences and preferences for adopting MBI among patients prescribed buprenorphine in office-based opioid treatment (OBOT). METHODS: This 23-item, semistructured cross-sectional survey was administered by study staff to patients enrolled in OBOT (N = 72) and consisted of demographic and clinical characteristics, perceptions, experiences with MBI, and preferred strategies to access MBI to support their treatment on buprenorphine. RESULTS: Most participants reported practicing at least 1 category of MBI (90.3%) on at least a daily (39.6%) or weekly (41.7%) basis including (1) spiritual meditation (eg, centering prayer; 67.7%); (2) nonmantra meditation (eg, comfortable posture; 61.3%); (3) mindfulness meditation (eg, mindfulness-based stress reduction; 54.8%); and (4) mantra meditation (eg, transcendental meditation; 29.0%). Interest in MBI was motivated by improving one's general health and well-being (73.4%), treatment outcomes with medications for OUD (eg, buprenorphine; 60.9%), and relationships with others (60.9%). Perceived clinical benefits of MBI included reduced anxiety or depression symptoms (70.3%), pain (62.5%), illicit substance or alcohol use (60.9%), cravings for illicit substances (57.8%), and opioid-related withdrawal symptoms (51.6%). CONCLUSIONS: Findings from this study indicate high acceptability for adopting MBI among patients prescribed buprenorphine in OBOT. Further research is needed to assess the efficacy of MBI to improve clinical outcomes among patients initiating buprenorphine in OBOT.


Assuntos
Buprenorfina , Meditação , Transtornos Relacionados ao Uso de Opioides , Humanos , Buprenorfina/uso terapêutico , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos
7.
J Addict Med ; 17(5): e281-e286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37788603

RESUMO

BACKGROUND: Pragmatic innovations are needed to optimize clinical outcomes among people who use opioids initiating buprenorphine. This pilot randomized controlled trial assessed the feasibility of integrating text messaging in a low threshold telebuprenorphine bridge program for people who use opioids during the COVID-19 pandemic. METHODS: Eligible adult patients with opioid use disorder inducted on buprenorphine (N = 128) in the NYC Health+Hospitals Virtual Buprenorphine Clinic between May and November 2020 were randomized to an automated texting intervention based on the medical management model versus treatment as usual. A participant feedback survey was administered at 8 weeks (n = 18). Primary outcomes consisted of acceptability (eg, study enrollment, engagement with the intervention) and feasibility (eg, lack of phone number and/or mobile phone ownership) of integrating texting in clinical care. A secondary outcome included retention in treatment at week 8 (ie, active buprenorphine prescription within the prior 7 days). RESULTS: Nearly all eligible patients consented to enroll in the study (90.8%) and few were excluded because of lack of mobile phone ownership (n = 27, 14.6%). Requests to discontinue receipt of texts (n = 6, 9.4%) was attributed to excessive message frequency, perceived lack of relevancy, and reduced interest in the intervention. Respondents completing the follow-up feedback survey were generally satisfied with the frequency of software-generated messages (14/18, 77.8%) and half shared text content with peers (9/18, 50%). There were no perceived issues with privacy, intrusiveness, or ease of use. Retention did not differ between participants randomized to the texting (M = 5.23 weeks, SD = 3.41) and treatment as usual groups (M = 4.98 weeks, SD = 3.34) at week 8 ( P = 0.676). CONCLUSIONS: This pilot randomized controlled trial confirms high acceptability and feasibility of integrating an automated texting tool in a telebuprenorphine bridge program. Future studies should assess whether text messaging may be efficacious when combined with staff contact and content addressing social determinants of health.


Assuntos
Buprenorfina , COVID-19 , Telefone Celular , Transtornos Relacionados ao Uso de Opioides , Envio de Mensagens de Texto , Adulto , Humanos , Projetos Piloto , Cidade de Nova Iorque , Pandemias , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Buprenorfina/uso terapêutico
8.
J Addict Med ; 17(5): 618-620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37788622

RESUMO

OBJECTIVES: Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. METHODS: We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. RESULTS: In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. CONCLUSIONS: Negative TLFB seems to be generally associated with negative results on urine toxicology.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Autorrelato , Ensaios Clínicos como Assunto , Estudos Multicêntricos como Assunto
10.
Am J Addict ; 32(3): 291-300, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36645265

RESUMO

BACKGROUND AND OBJECTIVES: To inform clinical practice, we identified subgroups of adults based on levels of depression symptomatology over time during opioid use disorder (OUD) treatment. METHODS: Participants were 474 adults in a 24-week treatment trial for OUD. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D) at nine-time points. This was a secondary analysis of the Clinical Trials Network Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (XBOT) trial using a growth mixture model. RESULTS: Three distinct depression trajectories were identified: Class 1 High Recurring-10% with high HAM-D with initial partial reductions (of HAM-D across time), Class 2 Persistently High-5% with persistently high HAM-D, and Class 3 Low Declining-85% of the participants, with low HAM-D with early sustained reductions. The majority (low declining) had levels of depression that improved in the first 4 weeks and then stabilized across the treatment period. In contrast, 15% (high recurring and persistently high) had high initial levels that were more variable across time. The persistently high class had higher rates of opioid relapse. DISCUSSION AND CONCLUSIONS: In this OUD sample, most depressive symptomatology was mild and improved after medication treatment for opioid use disorder (MOUD). Smaller subgroups had higher depressive symptoms that persisted or recurred after the initiation of MOUD. Depressive symptoms should be followed in patients initiating treatment for OUD, and when persistent, should prompt further evaluation and consideration of antidepressant treatment. SCIENTIFIC SIGNIFICANCE: This study is the first to identify three distinct depression trajectories among a large clinical sample of individuals in MOUD treatment.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Analgésicos Opioides/uso terapêutico , Depressão/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Naltrexona/uso terapêutico , Buprenorfina/uso terapêutico
11.
Addiction ; 118(3): 459-467, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36305669

RESUMO

BACKGROUND AND AIMS: Opioid overdose is a leading cause of death during the immediate time after release from jail or prison. Most jails in the United States do not provide methadone and buprenorphine treatment for opioid use disorder (MOUD), and research in estimating its impact in jail settings is limited. We aimed to test the hypothesis that in-jail MOUD is associated with lower overdose mortality risk post-release. DESIGN, SETTING AND PARTICIPANTS: Retrospective, observational cohort study of 15 797 adults with opioid use disorder who were released from New York City jails to the community in 2011-2017. They experienced 31 382 incarcerations and were followed up to 1 year. MEASUREMENTS: The primary outcomes were death caused by accidental drug poisoning and all-cause death. The exposure was receipt of MOUD (17 119 events) versus out-of-treatment (14 263 events) during the last 3 days before community re-entry. Covariates included demographic, clinical, behavioral, housing, health-care utilization and legal characteristics variables. We performed a multivariable, mixed-effect Cox regression analysis to test association between in-jail MOUD and deaths. FINDINGS: The majority were male (82%) and their average age was 42 years. Receiving MOUD was associated with misdemeanor charges, being female, injection drug use and homelessness. During 1 year post-release, 111 overdose deaths occurred and crude death rates were 0.49 and 0.83 per 100 person-years for in-jail MOUD and out-of-treatment groups, respectively. Accounting for confounding and random effects, in-jail MOUD was associated with lower overdose mortality risk [adjusted hazard ratio (aHR) = 0.20, 95% confidence interval (CI) = 0.08-0.46] and all-cause mortality risk (aHR = 0.22, 95% CI = 0.11-0.42) for the first month post-release. CONCLUSIONS: Methadone and buprenorphine treatment for opioid use disorder during incarceration was associated with an 80% reduction in overdose mortality risk for the first month post-release.


Assuntos
Buprenorfina , Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Adulto , Masculino , Humanos , Feminino , Estados Unidos , Metadona/uso terapêutico , Buprenorfina/uso terapêutico , Prisões Locais , Estudos Retrospectivos , Cidade de Nova Iorque/epidemiologia , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/terapia , Analgésicos Opioides/uso terapêutico
12.
Health Justice ; 10(1): 35, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36529829

RESUMO

While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical.

13.
Proc Natl Acad Sci U S A ; 119(50): e2211217119, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36469788

RESUMO

Most new pathogens of humans and animals arise via switching events from distinct host species. However, our understanding of the evolutionary and ecological drivers of successful host adaptation, expansion, and dissemination are limited. Staphylococcus aureus is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide. Here we trace the evolutionary history of bovine S. aureus using a global dataset of 10,254 S. aureus genomes including 1,896 bovine isolates from 32 countries in 6 continents. We identified 7 major contemporary endemic clones of S. aureus causing bovine mastitis around the world and traced them back to 4 independent host-jump events from humans that occurred up to 2,500 y ago. Individual clones emerged and underwent clonal expansion from the mid-19th to late 20th century coinciding with the commercialization and industrialization of dairy farming, and older lineages have become globally distributed via established cattle trade links. Importantly, we identified lineage-dependent differences in the frequency of host transmission events between humans and cows in both directions revealing high risk clones threatening veterinary and human health. Finally, pangenome network analysis revealed that some bovine S. aureus lineages contained distinct sets of bovine-associated genes, consistent with multiple trajectories to host adaptation via gene acquisition. Taken together, we have dissected the evolutionary history of a major endemic pathogen of livestock providing a comprehensive temporal, geographic, and gene-level perspective of its remarkable success.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Feminino , Humanos , Bovinos , Animais , Staphylococcus aureus/genética , Gado/genética , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/genética , Genoma , Especificidade de Hospedeiro
14.
Drug Alcohol Depend ; 241: 109657, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332588

RESUMO

BACKGROUND: Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions. AIM: Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes. METHODS: PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources. RESULTS: The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome. CONCLUSION: This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Tratamento de Substituição de Opiáceos/métodos , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/reabilitação , Buprenorfina/uso terapêutico , Metadona/uso terapêutico , Naltrexona/uso terapêutico
15.
BMC Bioinformatics ; 23(1): 416, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209064

RESUMO

BACKGROUND: The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation. RESULTS: Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences. CONCLUSIONS: We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.


Assuntos
Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Bactérias/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos
16.
Subst Use Misuse ; 57(11): 1732-1742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35975917

RESUMO

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
18.
J Subst Abuse Treat ; 143: 108830, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35773113

RESUMO

OBJECTIVE: Polysubstance use may complicate treatment outcomes for individuals who use opioids. This research aimed to examine the prevalence of polysubstance use in an opioid use disorder treatment trial population and polysubstance use's association with opioid relapse and craving. METHODS: This study is a secondary data analysis of individuals with opioid use disorder who received at least one dose of medication (n = 474) as part of a 24-week, multi-site, open label, randomized Clinical Trials Network study (CTN0051, X:BOT) comparing the effectiveness of extended-release naltrexone versus buprenorphine. Models examined pretreatment polysubstance use and polysubstance use during the initial 4 weeks of treatment on outcomes of relapse by week 24 of the treatment trial and opioid craving. RESULTS: Polysubstance use was generally not associated with treatment outcomes of opioid relapse and craving. Proportion of days of pretreatment sedative use was associated with increased likelihood of opioid relapse (OR: 1.01, 95 % CI: 1.00-1.02). Proportion of days of cocaine use during the initial 4 weeks of treatment was associated with increased likelihood of opioid relapse (OR: 1.05, 95 % CI: 1.01-1.09) but this effect was no longer significant once the potential of confounding by opioid use was considered. Sedative use during initial 4 weeks of treatment was associated with increased opioid craving (b: 0.77, 95 % CI: 0.01-1.52). The study found no other significant relationships. CONCLUSIONS: In the current study population, polysubstance use was only marginally associated with 24-week treatment outcomes.


Assuntos
Antagonistas de Entorpecentes , Transtornos Relacionados ao Uso de Opioides , Humanos , Antagonistas de Entorpecentes/uso terapêutico , Analgésicos Opioides/uso terapêutico , Prevalência , Preparações de Ação Retardada/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Naltrexona/uso terapêutico , Resultado do Tratamento , Injeções Intramusculares , Recidiva , Hipnóticos e Sedativos/uso terapêutico
19.
Nucleic Acids Res ; 50(9): 5191-5207, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35544231

RESUMO

Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into 'defence islands', providing a potentially synergistic level of protection against a wider range of assailants. However, there is a comparative paucity of information on how expression of these defence systems is controlled. Here, we functionally characterize a transcriptional regulator, BrxR, encoded within a recently described phage defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a combination of reporters and electrophoretic mobility shift assays, we discovered that BrxR acts as a repressor. We present the structure of BrxR to 2.15 Å, the first structure of this family of transcription factors, and pinpoint a likely binding site for ligands within the WYL-domain. Bioinformatic analyses demonstrated that BrxR-family homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localized with a diverse array of known phage defence systems, either alone or clustered into defence islands. BrxR is a novel regulator that reveals a common mechanism for controlling the expression of the bacterial phage defence arsenal.


Assuntos
Bactérias , Fatores de Transcrição , Bactérias/genética , Bactérias/metabolismo , Bactérias/virologia , Bacteriófagos/genética , Ilhas Genômicas/genética , Plasmídeos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Drug Alcohol Depend ; 236: 109469, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35605529

RESUMO

BACKGROUND: Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use. METHODS: Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use. RESULTS: Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time. CONCLUSION: In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02032433).


Assuntos
Buprenorfina , Metanfetamina , Transtornos Relacionados ao Uso de Opioides , Buprenorfina/uso terapêutico , Combinação Buprenorfina e Naloxona/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Metanfetamina/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
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