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Treatment with extended-release naltrexone: Risk of relapse to addictive substances and need of treatment duration in opioid dependent patients
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Avhengighet av opioider betraktes som en kronisk tilbakevendende lidelse som medfører økt risiko for tilbakefall og overdosedødsfall. Å utvide tilgangen til behandling for avhengighet er en vesentlig del av en helhetlig respons. Den mest brukte behandlingsmetoden for opioidavhengighet er legemiddelassistert rehabilitering (LAR), som inkluderer metadon og buprenorfin. Et alternativ til denne metoden er fullstendig avrusning og oppstart på opioid-beskyttende medisiner, slik som langtidsvirkende naltrekson. Denne medisinen er en fullstendig opioidantagonist og tilbyr farmakologisk beskyttelse mot tilbakefall og overdose. En injeksjon med langtidsvarende naltrekson gir beskyttelse som varer i en måned.
I denne studien har vi undersøkt risikoen for tilbakefall til heroin og andre ulovlige opioider hos pasienter med opioidavhengighet som ble behandlet med enten langtidsvirkende naltrekson eller daglig buprenorfin. I tillegg undersøkte vi eventuelle kompenserende økninger i forbruket av ulovlige stoffer utover opioider samt alkohol under både en randomisert klinisk studie og en påfølgende oppfølgingsstudie. Gitt mangelen på langtidsdata om XR-NTX og fraværet av etablerte retningslinjer for nødvendig behandlingsvarighet, hadde studien vår også som mål å fastslå pasientenes opplevde behov for forlenget behandling med XR-NTX og å vurdere resultatene av slik utvidet terapi.
Metode
Vi gjennomførte en åpen, randomisert klinisk studie ved fem urbane klinikker for behandling av avhengighet og avgiftning i Norge. Pasientene ble tilfeldig tildelt enten intramuskulær injeksjon med langtidsvirkende naltrekson eller daglig buprenorfin med nalokson, plassert under tungen, i en periode på 12 uker, med mulighet for å fortsette behandlingen med langtidsvirkende naltrekson i ytterligere 36 uker. Etter dette ble det satt i gang en prospektiv kohortstudie som fulgte opp ettårsstudien av XR-NTX, der pasientene kunne velge å fortsette behandlingen med XR-NTX etter eget ønske i opptil 104 uker.
Resultater
I artikkel II presenterte vi funn fra en studie hvor 58 pasienter fullførte det opprinnelige studiet på 48 uker, og av disse ønsket 50 å fortsette behandlingen med XR-NTX. Gjennomsnittlig behandlingstid var 44 uker, denne varierte fra 8 til 104 uker. Av alle pasientene rapporterte 70% at de ikke hadde brukt opioider i løpet av studien, og tilfredsheten med behandlingen, samt sannsynligheten for å anbefale behandlingen til andre var veldig høy. Gjennomsnittlig trang eller «sug» til opioider var svært lav gjennom hele studien. Det ble ikke rapportert om alvorlige bivirkninger blant pasientene i de første tre månedene etter at studien var avsluttet. Artikkel III viste at risikoen for første tilbakefall og risikoen for tilbakefall generelt til heroin og andre ulovlige opioider begge var betydelig lavere i XR-NTX-gruppen sammenlignet med BP-NLX-gruppen. I oppfølgingsstudien, der alle deltakende pasienter mottok XR-NTX, var risikoen for tilbakefall lav og stabil i begge grupper. Artikkel IV viste at det ikke var tydelige forskjeller mellom de to randomiserte gruppene når det gjaldt risiko for første tilbakefall til alkohol, amfetamin, benzodiazepiner eller cannabis. Vi fant de samme resultatene i oppfølgingsstudien mellom de som fortsatte med XRNTX og de som byttet til XR-NTX etter 12 ukers perioden. Det var heller ingen tydelig sammenheng mellom første tilbakefall til ulovlige opioider og første tilbakefall til ikke-opioide avhengighetsskapende stoffer. I begge studieperiodene var gjennomsnittlig tid i studien lengre blant de som fikk tilbakefall til ikke-opioide avhengighetsskapende stoffer enn de som ikke gjorde det.
Konklusjon
Funnene fra disse studiene dokumenterer hvor effektiv XR-NTX er i langtidsbehandling av opioidavhengighet. Det er verd å legge merke til at en stor andel av pasientene valgte å fortsette behandlingen med langtidsvirkende naltrekson, noen opptil 104 uker, noe som understreker aksepten av denne medisinen blant pasientene. Dette valget blir ytterligere bekreftet av den betydelige andelen som ikke hadde brukt opioider (70%), kombinert med høy behandlingstilfredshet og en markant reduksjon i trang etter opioider.
I tillegg viste den sammenlignende analysen en betydelig redusert risiko for tilbakefall til heroin og annen ulovlig opioidbruk i XR-NTX-gruppen sammenlignet med BP-NLX-gruppen, noe som bekrefter XR-NTX sin overlegne effektivitet i å forebygge opioidtilbakefall. Denne lave risikoen varte ved også under oppfølgingsfasen der alle deltakerne mottok XR-NTX; en konsekvent lav og stabil risiko for tilbakefall.
Langtidsvirkende naltrekson er effektivt i langtidsbehandling av opioidavhengighet, og viser lave tilbakefallsrater og høy behandlingstilfredshet blant pasienter. Disse resultatene taler for en bredere bruk av XR-NTX i behandling av opioidavhengighet.Background
Opioid dependence is considered a chronic relapsing disorder that carries an increased risk of repeated intoxication and overdose deaths, and expanding access to addiction treatment is an essential component of a comprehensive response. The most used therapeutic modality for opioid addiction is opioid agonist treatment (OAT), including methadone and buprenorphine. An alternative to this approach is complete detoxification and induction to antagonist medication, like extended-release naltrexone (XR-NTX). This medication is a full opioid antagonist and offers pharmacological protection against relapse, re-dependence and overdose. An injection with XR-NTX lasts for one month.
We investigated the relapse risk to heroin and other illicit opioids among patients with opioid dependence treated with either XR-NTX or BP-NLX. Additionally, we evaluated any compensatory increases in the consumption of non-opioid illicit substances and alcohol during both a randomised clinical trial and a subsequent follow-up study. Given the paucity of long-term data on XR-NTX and the absence of established guidelines regarding the necessary duration of treatment, our study also aimed to ascertain patients' perceived need for prolonged treatment with XR-NTX and to assess the outcomes of such extended therapy.
Methods
We conducted a multicentre, open-label randomised clinical trial across five urban addiction treatment and detoxification clinics in Norway. Patients were randomised to receive either intramuscular extended-release naltrexone hydrochloride (380 mg/month) or daily sublingual buprenorphine-naloxone (8-24/2-6 mg) for a duration of 12 weeks, with an option to continue treatment with extended-release naltrexone for an additional 36 weeks. Subsequently, a prospective cohort study was initiated following the one-year study of XR-NTX, wherein patients could opt to continue receiving XR-NTX treatment at their discretion for up to 104 weeks.
Results
Paper II presented findings showed that of the 58 patients who finished the parent study, 50 wanted to continue their treatment with XR-NTX, with a median prolonged treatment time of 44 weeks, ranging from 8-104 weeks. Of all the patients 70% reported no use of opioids during the study, and the mean scores for treatment satisfaction and recommending treatment to others were very high. The mean opioid craving score was very low throughout the study. No serious adverse events were reported among the patients during the first three months after study completion. Paper III reports that the risk of first relapse and risk of any relapse to heroin and other illicit opioids were both significantly lower in the XR-NTX group compared with the BP-NLX group. In the follow-up, where all participating patients received XR-NTX, the risk of relapse was low and stable in both groups. Paper IV showed that there were no significant differences between the two randomised groups in the risk of first relapse to alcohol, amphetamines, benzodiazepines, or cannabis. We found the same results in the follow-up between those continuing XR-NTX and those switching to XR-NTX after the trial period. There was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances. In both study periods, the mean time in the study was longer among those relapsing to nonopioid addictive substances than those who did not.
Conclusion
The findings from these studies provide robust evidence supporting the effectiveness of extended-release naltrexone (XR-NTX) in the long-term treatment of opioid use dependence. Notably, a significant proportion of patients chose to continue with XR-NTX treatment, some for up to 104 weeks, underscoring its acceptability among patients. This choice is further strengthened by the substantial abstinence rate (70%) from opioids observed, coupled with high treatment satisfaction and a marked reduction in opioid cravings. Additionally, the comparative analysis revealed a significantly reduced risk of relapse to heroin and other illicit opioid use in the XRNTX group compared to the BP-NLX group, affirming XR-NTX's superior efficacy in preventing opioid relapse. This was consistent even during the follow-up phase where all participants received XR-NTX, with a consistently low and stable risk of relapse.
Extended-release naltrexone is effective in the long-term management of opioid dependence, demonstrating low relapse rates and high treatment satisfaction among patients. These results advocate for the broader adoption of XR-NTX in opioid dependence treatment protocols, considering its benefits in maintaining sobriety and quality of life for affected individuals.Doktorgradsavhandlin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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