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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Recommandations pour la prise en charge de l'infection par le virus de l'hépatite C chez les usagers de drogues par injection. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 111:101669. [PMID: 26847504 DOI: 10.1016/j.drugpo.2015.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Hasselt University, Hasselt, Belgium
| | | | - Alessio Aghemo
- A.M. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Markus Backmund
- Ludwig-Maximilians-University, Munich, Germany; Praxiszentrum im Tal Munich, Munich, Germany
| | | | - Jude Byrne
- International Network of People who Use Drugs, Canberra, Australia
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew Hickman
- School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Achim Kautz
- European Liver Patients Association, Cologne, Germany
| | - Alain Litwin
- Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Andrew R Lloyd
- Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Maria Prins
- Department of Research, Cluster Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, CINIMA, Academic Medical Centre, Amsterdam, The Netherlands
| | - Tracy Swan
- Treatment Action Group, New York, United States
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany; Department of Psychiatry and Psychotherapy-CCM, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI, United States
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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Empfehlungen zur Hepatitis Versorgung bei Drogenkonsumierenden. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 111:101670. [PMID: 26749563 DOI: 10.1016/j.drugpo.2015.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Hasselt University, Hasselt, Belgium
| | | | - Alessio Aghemo
- A.M. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Markus Backmund
- Ludwig-Maximilians-University, Munich, Germany; Praxiszentrum im Tal Munich, Munich, Germany
| | | | - Jude Byrne
- International Network of People who Use Drugs, Canberra, Australia
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew Hickman
- School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Achim Kautz
- European Liver Patients Association, Cologne, Germany
| | - Alain Litwin
- Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Andrew R Lloyd
- Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Maria Prins
- Department of Research, Cluster Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, CINIMA, Academic Medical Centre, Amsterdam, The Netherlands
| | - Tracy Swan
- Treatment Action Group, New York, United States
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany; Department of Psychiatry and Psychotherapy-CCM, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI, United States
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Yevoo PE, Maffei A. Women in Neuroscience: Four Women’s Contributions to Science and Society. Front Integr Neurosci 2022; 15:810331. [PMID: 35153689 PMCID: PMC8825414 DOI: 10.3389/fnint.2021.810331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 12/27/2021] [Indexed: 11/24/2022] Open
Abstract
There has been increased cognizance of gender inequity and the importance of an inclusive and diverse approach to scientific research in recent years. However, the innovative work of women scientists is still undervalued based on reports of fewer women in leadership positions, limited citations of research spearheaded by women, reduced federal grant awards, and lack of recognition. Women have been involved in trailblazing work that paved the way for contemporary scientific inquiry. The strides made in current neuroscience include contributions from women who deserve more recognition. In this review, we discuss the work of four women whose groundbreaking scientific work has made ineffaceable marks in the neuroscience field. These women are pioneers of research and innovators and, in addition, contribute to positive change that bolsters the academic community and society. This article celebrates these women scientists, their substantial impacts in neuroscience, and the positive influence of their work on advancing society and culture.
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Affiliation(s)
- Priscilla E. Yevoo
- Department of Neurobiology and Behavior, SUNY – Stony Brook, Stony Brook, NY, United States
- Graduate Program in Neuroscience, SUNY – Stony Brook, Stony Brook, NY, United States
- *Correspondence: Priscilla E. Yevoo,
| | - Arianna Maffei
- Department of Neurobiology and Behavior, SUNY – Stony Brook, Stony Brook, NY, United States
- Graduate Program in Neuroscience, SUNY – Stony Brook, Stony Brook, NY, United States
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Dennis BB, Akhtar D, Cholankeril G, Kim D, Sanger N, Hillmer A, Chawar C, D'Elia A, Panesar B, Worster A, Marsh DC, Thabane L, Samaan Z, Ahmed A. The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study. Drug Alcohol Depend 2020; 209:107917. [PMID: 32088589 DOI: 10.1016/j.drugalcdep.2020.107917] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 02/08/2020] [Accepted: 02/11/2020] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear. AIM To determine whether CLD is associated with poor response to methadone treatment. METHODS Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model. RESULTS CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001). CONCLUSION CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.
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Affiliation(s)
- Brittany B Dennis
- Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton ON L8S4L8, Canada; Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - Daud Akhtar
- Department of Medicine, University of British Columbia, Vancouver Costal Health, Vancouver Canada.
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - Nitika Sanger
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada.
| | - Alannah Hillmer
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada.
| | - Caroul Chawar
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada.
| | - Alessia D'Elia
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada.
| | - Balpreet Panesar
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada.
| | - Andrew Worster
- Department of Health Research Evaluation and Impact (Formerly Department of Clinical Epidemiology and Biostatistics), McMaster University, Hamilton ON L8S4L8, Canada.
| | - David C Marsh
- Northern Ontario School of Medicine, Sudbury ON P3E2C6, Canada; Canadian Addiction Treatment Centres, Markham ON L3T 7P6, Canada.
| | - Lehana Thabane
- Department of Health Research Evaluation and Impact (Formerly Department of Clinical Epidemiology and Biostatistics), McMaster University, Hamilton ON L8S4L8, Canada; Centre for Evaluation of Medicine, Hamilton ON L8S4L8, Canada.
| | - Zainab Samaan
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton ON L8S4L8, Canada; McMaser Neuroscience Graduate Program, McMaster University, Hamilton ON, L8S4L8, Canada; Department of Health Research Evaluation and Impact (Formerly Department of Clinical Epidemiology and Biostatistics), McMaster University, Hamilton ON L8S4L8, Canada; Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton ON L8S4L8, Canada.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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Amraei M, Mohamadpour M, Ahmadi MRH, Azizi M, Daemi A, Omidi M, Shirzadpour E. Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:3785-3795. [PMID: 30464409 PMCID: PMC6225910 DOI: 10.2147/dddt.s182032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background Methadone (MET)-based treatment is currently one of the best known approaches in the treatment of opioid dependence. It is claimed that MET use exerts adverse effects on the performance of some organs, especially liver. Thus, the present study aims to investigate MET effects on the hepatic tissue as well as its effect on the hepatic enzyme levels and inflammatory markers in rats. Materials and methods Twenty-eight mature male Wistar rats underwent an 8-week treatment in four equal groups including the control group (an ordinary daily dietary regime) as well as the experimental groups 1, 2, and 3 (an ordinary daily dietary regime and gavage-fed on MET syrup for 5, 20, and 40 mg/kg body weight per day). Blood samples were collected from all rats in the beginning and end of the study to measure their hepatic enzyme levels and inflammatory markers. In the end, their livers were subjected to histological examinations. Results The mean serum levels of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) increased considerably across all the three groups that had received various dosages of MET (5, 20, and 40 mg/kg) in the end of the study as compared to the beginning of the study (P<0.001). It was also found that the inflammatory indicators (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein) rose significantly in the groups that had received various dosages of MET in contrast to the control group (P<0.01, P<0.001, and P<0.001, respectively). The histopathological images of the liver cross-sections revealed dosage-dependent tissue changes in the groups that had received various dosages of MET. Conclusion The present study tried to prove the adverse effects of MET in the development of liver damage. Since MET-based treatment is frequently prescribed by physicians for curing the addiction to narcotics, better strategies are required for its correct usage.
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Affiliation(s)
- Mansour Amraei
- Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Mahmoud Mohamadpour
- Department of Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran,
| | | | - Monireh Azizi
- Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Ahmad Daemi
- Department of Biochemistry, Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Mohammad Omidi
- Department of Biochemistry, Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Ehsan Shirzadpour
- Department of Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran,
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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Recomendaciones para el manejo de la infección por el virus de la hepatitis C entre usuarios de drogas por vía parenteral. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2015. [DOI: 10.1016/j.drugpo.2015.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Recommendations for the management of hepatitis C virus infection among people who inject drugs. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2015; 26:1028-38. [PMID: 26282715 PMCID: PMC6130980 DOI: 10.1016/j.drugpo.2015.07.005] [Citation(s) in RCA: 146] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 06/30/2015] [Accepted: 07/07/2015] [Indexed: 02/07/2023]
Abstract
In high income countries, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). In many low and middle income countries large HCV epidemics have also emerged among PWID populations. The burden of HCV-related liver disease among PWID is increasing, but treatment uptake remains extremely low. There are a number of barriers to care which should be considered and systematically addressed, but should not exclude PWID from HCV treatment. The rapid development of interferon-free direct-acting antiviral (DAA) therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near optimal efficacy with well-tolerated, short duration, all oral regimens. Further, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provide a framework for HCV assessment and care. Further research is needed to evaluate strategies to enhance testing, linkage to care, treatment, adherence, viral cure, and prevent HCV reinfection among PWID, particularly as new interferon-free DAA treatments for HCV infection become available.
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Affiliation(s)
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Hasselt University, Hasselt, Belgium
| | | | - Alessio Aghemo
- A.M. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Markus Backmund
- Ludwig-Maximilians-University, Munich, Germany; Praxiszentrum im Tal Munich, Munich, Germany
| | | | - Jude Byrne
- International Network of People who Use Drugs, Canberra, Australia
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew Hickman
- School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Achim Kautz
- European Liver Patients Association, Cologne, Germany
| | - Alain Litwin
- Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Andrew R Lloyd
- Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Maria Prins
- Department of Research, Cluster Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, CINIMA, Academic Medical Centre, Amsterdam, The Netherlands
| | - Tracy Swan
- Treatment Action Group, New York, United States
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany; Department of Psychiatry and Psychotherapy-CCM, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI, United States
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Arain A, Robaeys G. Eligibility of persons who inject drugs for treatment of hepatitis C virus infection. World J Gastroenterol 2014; 20:12722-12733. [PMID: 25278674 PMCID: PMC4177459 DOI: 10.3748/wjg.v20.i36.12722] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus (HCV) infection. Although people who inject drugs (PWID) are the major source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these patients, and substitution therapy and active substance use are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.
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Robaeys G, Grebely J, Mauss S, Bruggmann P, Moussalli J, De Gottardi A, Swan T, Arain A, Kautz A, Stöver H, Wedemeyer H, Schaefer M, Taylor L, Backmund M, Dalgard O, Prins M, Dore GJ. Recommendations for the management of hepatitis C virus infection among people who inject drugs. Clin Infect Dis 2014; 57 Suppl 2:S129-37. [PMID: 23884061 DOI: 10.1093/cid/cit302] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In the developed world, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). The burden of HCV-related liver disease in this group is increasing, but treatment uptake among PWID remains low. Among PWID, there are a number of barriers to care that should be considered and systematically addressed, but these barriers should not exclude PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provides a framework for HCV assessment, management, and treatment. Further research is needed to evaluate strategies to enhance assessment, adherence, and SVR among PWID, particularly as new treatments for HCV infection become available.
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Affiliation(s)
- Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium.
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10
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EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2014; 60:392-420. [PMID: 24331294 DOI: 10.1016/j.jhep.2013.11.003] [Citation(s) in RCA: 646] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023]
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Lohia P, Jinjuvadia R, May E. Profound jaundice in a patient with acute hepatitis C. BMJ Case Rep 2013; 2013:bcr2013200233. [PMID: 24031074 PMCID: PMC3794154 DOI: 10.1136/bcr-2013-200233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 52-year-old African-American woman with overall good health and medical history of asthma and depression presented with right lower quadrant abdominal pain, vomiting and icterus for 3 weeks. Her physical examination was remarkable for only sclera icterus and mild tenderness on palpation in the right lower quadrant. Investigations revealed marked hyperbilirubinemia and transaminitis, with other serological and radiological studies unremarkable and a hepatitis A, B and C panel negative 3 weeks before presentation. Repeat hepatitis panel showing hepatitis C antibody positive with viral load 20 739 524 IU/mL. Liver biopsy supported the diagnosis of acute hepatitis C infection.
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Affiliation(s)
- Prateek Lohia
- Department of Internal Medicine, Wayne State University School of Medicine/Detroit Medical Center, Detroit, Michigan, USA
| | - Raxitkumar Jinjuvadia
- Department of Internal Medicine, Wayne State University School of Medicine/Detroit Medical Center, Detroit, Michigan, USA
| | - Elizabeth May
- Department of Gastroenterology, Wayne State University School of Medicine/Detroit Medical Center, Detroit, Michigan, USA
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Jiao M, Greanya ED, Haque M, Yoshida EM, Soos JG. Methadone maintenance therapy in liver transplantation. Prog Transplant 2010. [PMID: 20929104 DOI: 10.7182/prtr.20.3.r8n4k17212158k62] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Cirrhosis due to chronic infection with hepatitis C virus remains by far the most common reason for liver transplantation in North America. Currently, parenteral use of street drugs is the most common means of acquiring hepatitis C. Methadone maintenance therapy is an accepted form of treatment for chronic opiate (eg, heroin) addiction and, not surprisingly, a significant proportion of methadone-treated patients have chronic hepatitis C. The feasibility of liver transplant candidacy in hepatitis patients who require methadone maintenance therapy is controversial, and some transplant centers require patients to withdraw from such therapy in order for the transplant process to move forward. Thus stable patients with end-stage cirrhosis who are receiving methadone maintenance are left in a most difficult situation: discontinue methadone and accept the side effects of withdrawal with the risk of recidivism to use of street opiates, an absolute contraindication for transplantation, or continue methadone therapy and risk exclusion from the transplant process. The issue of methadone replacement therapy in end-stage cirrhosis and the posttransplant literature on the subject are explored in this paper.
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Affiliation(s)
- Modi Jiao
- University of Toronto Scarborough, Toronto, Ontario
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Jiao M, Greanya ED, Haque M, Yoshida EM, Soos JG. Methadone Maintenance Therapy in Liver Transplantation. Prog Transplant 2010; 20:209-14; quiz 215. [DOI: 10.1177/152692481002000303] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Cirrhosis due to chronic infection with hepatitis C virus remains by far the most common reason for liver transplantation in North America. Currently, parenteral use of street drugs is the most common means of acquiring hepatitis C. Methadone maintenance therapy is an accepted form of treatment for chronic opiate (eg, heroin) addiction and, not surprisingly, a significant proportion of methadone-treated patients have chronic hepatitis C. The feasibility of liver transplant candidacy in hepatitis patients who require methadone maintenance therapy is controversial, and some transplant centers require patients to withdraw from such therapy in order for the transplant process to move forward. Thus stable patients with end-stage cirrhosis who are receiving methadone maintenance are left in a most difficult situation: discontinue methadone and accept the side effects of withdrawal with the risk of recidivism to use of street opiates, an absolute contraindication for transplantation, or continue methadone therapy and risk exclusion from the transplant process. The issue of methadone replacement therapy in end-stage cirrhosis and the posttransplant literature on the subject are explored in this paper.
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Affiliation(s)
- Modi Jiao
- University of Toronto Scarborough, Toronto, Ontario (MJ), Vancouver General Hospital (EDG, JGS), University of British Columbia (MH, EMY), British Columbia Transplant (MJ, EDG, MH, EMY, JGS), Vancouver, BC
| | - Erica D. Greanya
- University of Toronto Scarborough, Toronto, Ontario (MJ), Vancouver General Hospital (EDG, JGS), University of British Columbia (MH, EMY), British Columbia Transplant (MJ, EDG, MH, EMY, JGS), Vancouver, BC
| | - Mazhar Haque
- University of Toronto Scarborough, Toronto, Ontario (MJ), Vancouver General Hospital (EDG, JGS), University of British Columbia (MH, EMY), British Columbia Transplant (MJ, EDG, MH, EMY, JGS), Vancouver, BC
| | - Eric M. Yoshida
- University of Toronto Scarborough, Toronto, Ontario (MJ), Vancouver General Hospital (EDG, JGS), University of British Columbia (MH, EMY), British Columbia Transplant (MJ, EDG, MH, EMY, JGS), Vancouver, BC
| | - John G. Soos
- University of Toronto Scarborough, Toronto, Ontario (MJ), Vancouver General Hospital (EDG, JGS), University of British Columbia (MH, EMY), British Columbia Transplant (MJ, EDG, MH, EMY, JGS), Vancouver, BC
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Roche DJ, Childs E, Epstein AM, King AC. Acute HPA axis response to naltrexone differs in female vs. male smokers. Psychoneuroendocrinology 2010; 35:596-606. [PMID: 19837518 PMCID: PMC2843791 DOI: 10.1016/j.psyneuen.2009.09.016] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2009] [Revised: 07/14/2009] [Accepted: 09/17/2009] [Indexed: 01/28/2023]
Abstract
BACKGROUND Both opioid antagonist administration and cigarette smoking acutely increase hypothalamic-pituitary-adrenal (HPA) axis activity as measured by adrenocorticotropic hormone (ACTH) and cortisol levels. However, male and female smokers may differ in their response to the opioid antagonist naltrexone, which may be partially mediated by sex differences in HPA axis function. Smokers, as a group, have frequently been shown to have HPA axis dysfunction, which may have relevance to the course and maintenance of nicotine dependence. The purpose of this study was to examine possible sex differences in HPA axis function by comparing stress-hormone response to naltrexone within healthy male and female smokers. Additionally, exploratory analyses compared the combined effects of naltrexone and cigarette smoking on hormonal responsivity between the sexes. METHOD Thirty-eight healthy smokers (22 men) were tested in two separate morning sessions after 12h of smoking abstinence. For women, self-reports of menstrual cycle information were obtained prior to each session (date of last menstruation, cycle length, reproductive phase, etc.). Each participant received 50mg naltrexone or placebo capsule (in random order) and plasma levels of ACTH and cortisol were assessed at regular intervals for several hours. A subgroup of 12 participants underwent a similar, additional session in which they smoked a single cigarette three hours after naltrexone administration. RESULTS Naltrexone significantly increased ACTH and cortisol levels in women, but not men (DrugxSexxTime, p<0.05). A post hoc analysis suggested that women at an estimated 'high estrogen' phase had a greater cortisol response (DrugxEstrogen level, p<0.05) than those at an estimated 'low estrogen' phase. Exploratory analyses showed that smoking a single cigarette potentiated naltrexone-induced increases in ACTH (p<0.05) and cortisol (p<0.01) in all participants. CONCLUSION The findings support the hypothesis that women are more sensitive to opioid antagonism at the level of the HPA axis. Although further studies are needed to examine mechanisms underlying these responses, both results may have clinical implications for the use of naltrexone as a treatment for nicotine dependence.
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Affiliation(s)
- Daniel J.O. Roche
- Committee on Neurobiology, University of Chicago, 947 E. 58th St. Chicago, IL 60637
| | - Emma Childs
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Avenue Chicago, IL 60637, Chicago, IL
| | - Alyssa M. Epstein
- Department of Psychology, University of California at Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563
| | - Andrea C. King
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Avenue Chicago, IL 60637, Chicago, IL, Committee on Neurobiology, University of Chicago, 947 E. 58th St. Chicago, IL 60637,Corresponding author: Andrea King, Ph.D., TEL (773) 702-6181, FAX (773) 702-6454,
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Kreek MJ, Talal AH, Piccolo P. Treating chronic hepatitis C in recovering opiate addicts: yes, we can. Dig Liver Dis 2009; 41:308-10. [PMID: 19233749 PMCID: PMC2778039 DOI: 10.1016/j.dld.2009.01.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Accepted: 01/10/2009] [Indexed: 12/11/2022]
Affiliation(s)
- M J Kreek
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
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Kreek MJ, Schlussman SD, Reed B, Zhang Y, Nielsen DA, Levran O, Zhou Y, Butelman ER. Bidirectional translational research: Progress in understanding addictive diseases. Neuropharmacology 2008; 56 Suppl 1:32-43. [PMID: 18725235 PMCID: PMC2741728 DOI: 10.1016/j.neuropharm.2008.07.042] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2008] [Revised: 07/29/2008] [Accepted: 07/30/2008] [Indexed: 11/17/2022]
Abstract
The focus of this review is primarily on recent developments in bidirectional translational research on the addictions, within the Laboratory of the Biology of Addictive Diseases at The Rockefeller University. This review is subdivided into major interacting aspects, including (a) Investigation of neurobiological and molecular adaptations (e.g., in genes for the opioid receptors or endogenous neuropeptides) in response to cocaine or opiates, administered under laboratory conditions modeling chronic patterns of human self-exposure (e.g., chronic escalating "binge"). (b) The impact of such drug exposure on the hypothalamic-pituitary-adrenal (HPA) axis and interacting neuropeptidergic systems (e.g., opioid, orexin and vasopressin). (c) Molecular genetic association studies using candidate gene and whole genome approaches, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy. (d) Neuroendocrine challenge studies in normal volunteers and current addictive disease patients along with former addicts in treatment, to investigate differential pharmacodynamics and responsiveness of molecular targets, in particular those also investigated in the experimental and molecular genetic approaches as described above.
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Affiliation(s)
- M J Kreek
- Laboratory of the Biology of Addictive Diseases, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
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Abstract
AIMS Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. METHODS Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990-present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. RESULTS Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53-96%) and in patients enrolled in methadone maintenance programs (67-96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28-94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72-100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. CONCLUSION High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them.
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Bart G, Piccolo P, Zhang L, Jacobson I, Schaefer RA, Kreek MJ. Markers for hepatitis A, B and C in methadone maintained patients: an unexpectedly high co-infection with silent hepatitis B. Addiction 2008; 103:681-6. [PMID: 18339114 PMCID: PMC3810150 DOI: 10.1111/j.1360-0443.2008.02151.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
AIMS To determine the prevalence of hepatitis A, B and C viruses in patients attending a methadone maintenance clinic in New York City. DESIGN Cross-sectional. SETTING The Adult Services Clinic of Weill Cornell Medical College, an urban hospital-affiliated methadone program. PARTICIPANTS Former heroin addicted adults (n = 103) on methadone maintenance therapy. MEASUREMENTS Markers for hepatitis A virus [HAV immunoglobulin M (IgM) and imunoglobulin G (IgG)], hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb)] and hepatitis C virus (HCVAb). Serum alanine aminotransferase (ALT) and quantitative HCV RNA were also obtained. Qualitative detection of HBV DNA and HCV genotype were obtained in a subset of subjects. FINDINGS More than 40% of subjects had markers for all three viruses. HCVAb was the most prevalent (83.5%), followed by HBcAb (65.0%), HAV IgG (46.1%) and HBsAb (41.1%). Hepatitis C RNA was detected in 70.6% of HCVAb positive subjects. While no subject had HBsAg, HBV DNA was detected in 26.4% of subjects who underwent this measure; all (n = 20) had HBcAb as their only HBV marker. The presence of HBV DNA did not influence ALT. Subjects with HCV RNA had higher ALTs than those without HCV RNA. CONCLUSIONS Most methadone-maintained subjects had at least one marker for viral hepatitis, with 41.8% having markers for HAV, HBV and HCV. A quarter of subjects had silent HBV infection, defined as the presence of HBV DNA in the absence of HBsAg. These subjects should be considered infectious and pose a public health risk.
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Affiliation(s)
- Gavin Bart
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, NY, NY 10021, USA.
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19
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Abstract
The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug's original indication by the FDA. Such 'off-label' prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature. The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect.
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Affiliation(s)
- George A Kenna
- Department of Community Health, Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA.
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Asherson RA, Davidge-Pitts MC, Wypkema E. “Primary” antiphospholipid syndrome evolving into Waldenstrom’s macroglobulinaemia: a case report. Clin Rheumatol 2006; 26:278-80. [PMID: 16547696 DOI: 10.1007/s10067-005-0144-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2005] [Revised: 09/12/2005] [Accepted: 09/12/2005] [Indexed: 10/24/2022]
Abstract
A 57-year-old woman with a history of transient ischaemic attacks and six recurrent foetal losses accompanied by elevations of antiphospholipid antibodies was diagnosed as having a "primary" antiphospholipid syndrome. She was followed up for 5 years, and she developed anaemia, leucopenia and splenomegaly. A bone marrow trephine was diagnostic of Waldenstrom's macroglobulinaemia. A false positive serological test for syphilis was demonstrated and apparently had been noted in her second pregnancy more than 20 years prior to her presentation with an antiphospholipid syndrome. There had previously been no indication to perform serum electrophoretic studies. This case illustrates the importance of this investigation in any middle-aged patient presenting with an antiphospholipid syndrome and a monoclonal gammopathy This finding might presage the development of a more serious condition, even years later (as in our patient).
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Affiliation(s)
- R A Asherson
- Division Immunology, School of Pathology, University of the Witswatersrand, Johannesburg, 2000, South Africa.
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Neuman MG, Monteiro M, Rehm J. Drug interactions between psychoactive substances and antiretroviral therapy in individuals infected with human immunodeficiency and hepatitis viruses. Subst Use Misuse 2006; 41:1395-463. [PMID: 17002989 DOI: 10.1080/10826080600846235] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The liver disease characteristic of alcohol dependence encompasses three main related entities: steatosis, alcoholic hepatitis, and cirrhosis. Alcoholic cirrhosis is a leading cause of global morbidity and mortality. Alcohol intake among injecting drug users is a major contributor to transmission of viral infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C viruses (HCV). HIV and HCV coinfected patients develop liver diseases earlier and more severely than the monoinfected individuals, including hepatocellular carcinoma. Interactions exist between the therapeutic drugs used to minimize and control the drug and alcohol dependence. Furthermore, drug-drug interactions occur between the highly active antiretroviral therapy (HAART) and alcohol, different HAART components and methadone, or each one of the therapies with the other, thus contributing to a higher toxicity level. With the evolution of effective antiretroviral therapy, survival of persons with HIV, and the syndrome it causes, acquired immunodeficiency syndrome (AIDS) has increased dramatically. Drug-drug interactions may appear between alcohol and anti-HBV or anti-HCV, therapy in the presence or absence of anti-HIV therapy. Several other medical-, social-, and drug-related factors of this population have to be considered when providing HAART. Because many coinfected patients also have problems with substance use, dealing with their drug dependence is an important first step in an attempt to improve adherence to and tolerance of antiviral therapy. It is necessary to minimize the risk of liver disease acceleration and/or reinfection with hepatitis viruses. Knowledge of potential drug interactions between methadone, antiretroviral therapy, psychoactive drugs, and antipsychotics and the role of coinfection with HBV or HCV and the drugs used in eradicating viral hepatitis permits suitable antiretroviral combinations.
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Comparative Safety and Side Effect Profiles of Buprenorphine and Methadone in the Outpatient Treatment of Opioid Dependence. ADDICTIVE DISORDERS & THEIR TREATMENT 2005. [DOI: 10.1097/01.adt.0000145126.17405.6a] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Kreek MJ, Schlussman SD, Bart G, Laforge KS, Butelman ER. Evolving perspectives on neurobiological research on the addictions: celebration of the 30th anniversary of NIDA. Neuropharmacology 2004; 47 Suppl 1:324-44. [PMID: 15464148 DOI: 10.1016/j.neuropharm.2004.07.024] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2004] [Revised: 07/02/2004] [Accepted: 07/20/2004] [Indexed: 01/31/2023]
Abstract
The roots of the Laboratory of the Biology of the Addictive Diseases are in the development of methadone maintenance for the treatment of opiate addiction. Methadone maintenance therapy continues to be one of the major effective forms of addiction pharmacotherapy and underscores the importance of biological factors in the physiology and treatment of the addictive diseases. Recent work in the Laboratory has focused on the neurobiological, neurochemical, neuroendocrine and behavioral aspects of addictive diseases (principally cocaine and the opiate addictions), using an interdisciplinary approach. The models we have focused on range from in vitro molecular biology and neuroscience, to in vivo animal models, to experiments in normal human populations and patients with specific addictive diseases, and most recently to the human molecular genetics of different addictive diseases. Two long-term corollary hypotheses have guided the Laboratory's work: (1) That the endogenous opioid peptide/receptor systems play a central role in the addictive states and therefore in their treatment. (2) That atypical responsivity to stressors (e.g., in the hypothalamic-pituitary-adrenal axis) plays a role in vulnerability and relapse to specific addictive diseases. This atypical responsivity may be drug-induced, environmentally acquired, and/or due to genetic variation.
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Affiliation(s)
- Mary Jeanne Kreek
- Laboratory of the Biology of the Addictive Diseases, The Rockefeller University, 1230 York Avenue, Box 171, New York, NY 10021, USA.
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Muga R, Guardiola H, Rey-Joly C. [Evaluation of drug addicts with associated pathology. Clinical and therapeutic aspects of the integral attention]. Med Clin (Barc) 2004; 122:624-35. [PMID: 15142512 DOI: 10.1016/s0025-7753(04)74332-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
We review the evaluation and treatment of patients with drug addictions complicated by other acute or chronic diseases from the perspective of the hospital setting. The spectrum of drug addiction's complications is broad and in many instances it is predetermined by the abuse substance and its administration route. Some complications of intravenous drug addiction have dramatically decreased in the last few years as a result of a better knowledge of hygienic customs and after the implementation of some health interventions such as the provision of sterile injectable devices. Two highly prevalent infections --HIV/AIDS and hepatitis C-- remain from the period in which most HIV infections owed to the intravenous use of heroin. Of note, these two infections largely account for the survival and quality of life of those who quit their addiction. On the other hand, it is still common the hospitalization of patients with both alcohol dependence and intercurrent diseases in whom their drug addiction may pass unnoticed. Other common situations include the treatment of acute patients with cocaine addiction and psychiatric comorbidity, patients under methadone therapy and, in general, all those cases in which, in emergency, ordinary hospital wards and specialized units, a wide differential diagnosis is raised when there is a coexistence of signs and symptoms common to an addiction, infection and/or intoxication. An integral vision of drug addiction and its complications, as well as the clinical evaluation of all health problems, is fundamental for the prognosis and treatment of these patients.
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Affiliation(s)
- Roberto Muga
- Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Badalona, España.
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Kreek MJ, Vocci FJ. History and current status of opioid maintenance treatments: blending conference session. J Subst Abuse Treat 2002; 23:93-105. [PMID: 12220607 DOI: 10.1016/s0740-5472(02)00259-3] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Opiate addiction is a chronic, relapsing disorder. Left untreated, high morbidity and mortality rates are seen. Pharmacotherapies for this disorder using mu opiate agonists (methadone and levomethadyl acetate) and partial agonists have been developed in the last 40 years. Agonist pharmacotherapy with oral methadone for the treatment of opiate dependence was developed in clinical pharmacology studies at Rockefeller University by Dole, Nyswander, and Kreek. Further studies by this laboratory and others established that moderate to high dose treatment with methadone (80-120 mg) reduced or eliminated opiate use in outpatient settings with consequent reductions in morbidity and up to 4-fold reductions in mortality. Levomethadyl acetate (LAAM), a congener of methadone, is biotransformed to active metabolites responsible for its longer duration of action. The Federal Regulations regarding the dispensation of methadone and LAAM have recently been revised to facilitate the treatment of patients under a "medical maintenance" model. Future regulatory reform will likely involve the establishment of rules for "office based opioid treatment."
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Affiliation(s)
- Mary Jeanne Kreek
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University and The Rockefeller University Hospital, New York, NY 10021, USA
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Kreek MJ. Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci 2000; 909:186-216. [PMID: 10911931 DOI: 10.1111/j.1749-6632.2000.tb06683.x] [Citation(s) in RCA: 176] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and persistence of, as well as relapse to, use of addictive drugs.
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Affiliation(s)
- M J Kreek
- Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, New York 10021, USA.
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Borg L, Broe DM, Ho A, Kreek MJ. Cocaine abuse sharply reduced in an effective methadone maintenance program. J Addict Dis 2000; 18:63-75. [PMID: 10631964 DOI: 10.1300/j069v18n04_06] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
A comprehensive study of an urban methadone clinic with supervised urine analyses for illicit drugs was conducted over an 18 month period for a 133 patient cohort as they entered or remained in methadone maintenance for narcotic addiction. Overall retention during the study was 85%, with significantly (p < .05) higher daily methadone doses (mean 67.1 mg +/- 2.1) in those patients still in treatment at the end of the study. Predictably, illicit opioid use was dramatically reduced, to 10% as measured by urine toxicology in the last month of treatment. Moreover, significantly more patients stopped regular cocaine abuse (69%) than started using cocaine (10%, Fisher's exact test, p = .02). Thus, with effective methadone maintenance using adequate dosages, the majority of patients remain in treatment and reduce cocaine abuse as well as illicit opioid use, with implications for public health by reducing the spread of infectious diseases including hepatitis B, C, D and human immunodeficiency virus (HIV-1).
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Affiliation(s)
- L Borg
- Rockefeller University, The Laboratory of the Biology of Addictive Diseases, New York, NY 10021, USA.
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Contoreggi C, Rexroad VE, Lange WR. Current management of infectious complications in the injecting drug user. J Subst Abuse Treat 1998; 15:95-106. [PMID: 9561947 DOI: 10.1016/s0740-5472(97)00048-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs.
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Affiliation(s)
- C Contoreggi
- Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
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Abstract
Neurobiological and behavioral studies, as well as basic and applied clinical research studies, may all contribute to the development of a pharmacotherapy for a specific addictive disease. This paper reviews recent findings from research work, primarily from one laboratory along with collaborative laboratories, that could have some relevance for the development of pharmacotherapy for cocaine dependency. The much earlier experiences of this laboratory in the development of a pharmacotherapy for opiate addiction will be addressed in the context of providing both some specific suggestions for addictive disease pharmacotherapy development and some warnings about the complexities of the introduction and implementation of a pharmacotherapy once developed. Finally, based on both the earlier perspectives and the more recent research findings, some very specific, though speculative, suggestions will be made about the development of novel pharmacotherapies for early opiate addiction, especially for cocaine abuse or addiction and prevention of relapse to cocaine use. The complex and diverse nature of the challenge for pharmacotherapy for the addictive diseases is presented, including specifically a mandate for broadening educational efforts concerning the basis of addictive diseases and the need for treatment, in parallel with the scientific efforts to develop increasingly sophisticated and targeted pharmacotherapies.
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Affiliation(s)
- M J Kreek
- Laboratory on the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA
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31
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Kreek MJ. Clinical Update of Opioid Agonist and Partial Agonist Medications for the Maintenance Treatment of Opioid Addiction. ACTA ACUST UNITED AC 1997. [DOI: 10.1006/smns.1997.0114] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Brown LS, Sawyer RC, Li R, Cobb MN, Colborn DC, Narang PK. Lack of a pharmacologic interaction between rifabutin and methadone in HIV-infected former injecting drug users. Drug Alcohol Depend 1996; 43:71-7. [PMID: 8957145 DOI: 10.1016/s0376-8716(97)84352-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Rifampin, an agent known to decrease the half-life of methadone, and rifabutin are two rifamycins that are structurally similar and share mechanisms of action. Hence the possibility of a drug-drug interaction between rifabutin and methadone was evaluated in 24 methadone-maintained, former injecting drug users infected with the human immunodeficiency virus. The study was an open-label, drug-drug interaction and safety trial in which patients were followed for 15 days. Each patient received rifabutin 300 mg as a single dose concomitantly with their individualized methadone dosage. No significant differences in methadone peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, systemic clearance or renal clearance was observed in the presence of rifabutin. Seventy-five percent of the patients reported at least one symptom of narcotic withdrawal during the study, however, these symptoms were mild. A relationship between the development of narcotic withdrawal and methadone systemic exposure could not be established. Concurrent administration of rifabutin and methadone appeared to be safe in human immunodeficiency virus-infected injecting drug users maintained on stable doses of methadone and is not expected to produce any significant changes in the pharmacokinetics of methadone in these patients.
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Affiliation(s)
- L S Brown
- Addiction Research and Treatment Corporation, Brooklyn, NY 11201, USA
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Kreek MJ. Opioid receptors: some perspectives from early studies of their role in normal physiology, stress responsivity, and in specific addictive diseases. Neurochem Res 1996; 21:1469-88. [PMID: 8947936 DOI: 10.1007/bf02532387] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy for the treatment of heroin addiction in New York City, from 1960-1973, along with the special relationships between two leading scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective. The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early 1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies of the possible involvement of the specific opioid receptors in these three addictive diseases-heroin addiction, cocaine addiction and alcoholism-from our laboratory are discussed in a historical perspective of the development of these ideas from the early research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout the world.
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Affiliation(s)
- M J Kreek
- Laboratory on the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA
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34
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Gonzales GR, Portenoy RK. Selection of analgesic therapies in rheumatoid arthritis: the role of opioid medications. ARTHRITIS CARE AND RESEARCH : THE OFFICIAL JOURNAL OF THE ARTHRITIS HEALTH PROFESSIONS ASSOCIATION 1993; 6:223-8. [PMID: 7918718 DOI: 10.1002/art.1790060409] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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35
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Novick DM, Richman BL, Friedman JM, Friedman JE, Fried C, Wilson JP, Townley A, Kreek MJ. The medical status of methadone maintenance patients in treatment for 11-18 years. Drug Alcohol Depend 1993; 33:235-45. [PMID: 8261888 DOI: 10.1016/0376-8716(93)90110-c] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
To assess the safety and potential health consequences of long-term methadone maintenance treatment, we identified 111 male patients admitted to methadone maintenance treatment between 1965 and 1968, still enrolled in 1980 and in continuous treatment for at least 10 years. We were able, between 1980 and 1985, to examine patients or review records of 110 patients (99%). Most medical diagnoses, symptomatic complaints, physical examination findings and laboratory test results occurred with similar frequency in the long-term methadone maintenance patients and in a group of 56 long-term heroin addicts. These data suggest that prolonged methadone maintenance treatment is safe and is not associated with unexpected adverse effects.
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Affiliation(s)
- D M Novick
- Rockefeller University, New York, NY 10021
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36
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Abstract
Methadone maintenance therapy is advocated as a major preventive strategy for the spread of the human immunodeficiency virus (HIV) and other blood-borne infectious agents among injecting drug users (IDUs) because of its effects in decreasing the frequency of injecting and presumably sharing of equipment. As an opioid agonist, methadone may share the direct and indirect immunoregulatory effects of other opioids, and thus affect susceptibility to, and the natural history of, HIV infection. Available evidence pertaining to methadone and immune function is reviewed. The long-term immunosuppression observed in heroin injectors on present (incomplete) evidence appears to be caused by factors associated with a drug-using lifestyle rather than by a direct action of heroin. Although data are conflicting, it is most likely that methadone does not significantly impair immune function and is safe for HIV-infected IDUs, possibly even allowing some improvement of immune function to occur. The increasing reliance placed on methadone maintenance to control the epidemic of HIV infection in IDUs requires that remaining uncertainties regarding methadone and immune function are clarified urgently.
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Affiliation(s)
- C McLachlan
- Department of Psychology, School of Behavioural Sciences, Latrobe University, Bundoora, Victoria, Australia
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Abstract
Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. The management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular). Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other analgesic modalities in an anaesthesiology-based 'acute pain service'. The use of opioids for chronic pain of nonmalignant origin remains controversial. There is a perceived conflict between patients' interests and those of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called 'dual pharmacology'). With sensible guidelines, and in the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of chronic pain.
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Affiliation(s)
- S A Schug
- Pain Clinic, Auckland Hospital, New Zealand
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Doweiko JP, Nompleggi DJ. The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. JPEN J Parenter Enteral Nutr 1991; 15:476-83. [PMID: 1895489 DOI: 10.1177/0148607191015004476] [Citation(s) in RCA: 183] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted.
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Affiliation(s)
- J P Doweiko
- Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts
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39
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Abstract
Opioid dependence has been studied with regard to its effects on the woman, the fetus, and the child for the past three decades, and it continues to be a serious problem that must be recognized and addressed by the health care delivery system in order to provide optimal medical care. The use of pharmacotherapy, such as methadone maintenance treatment (MMT), is only one of a variety of treatment modalities to provide optimal services for opioid-dependent women. The complete schema for treating opioid dependence in the perinatal period is complex and intense, but MMT serves multiple purposes. Primarily, it removes the addicted woman from the drug-seeking environment, eliminates the necessary illicit behavior, and prevents the peaks and valleys in the maternal heroin level that may occur throughout the day. In addition, maternal nutrition is usually improved and MMT patients become amenable to prenatal care and psychosocial rehabilitation. It is evident from the findings of numerous studies that when the physical, psychological, and socioeconomic issues of pregnant opioid-dependent women and their children are coupled with MMT, the potential physical and behavioral effects of psychoactive drugs on the mother, the fetus, the newborn, and the child may be markedly reduced.
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Affiliation(s)
- L P Finnegan
- Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania
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40
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Novick DM, Ochshorn M, Kreek MJ. In vivo and in vitro studies of opiates and cellular immunity in narcotic addicts. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 1991; 288:159-70. [PMID: 1950730 DOI: 10.1007/978-1-4684-5925-8_18] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- D M Novick
- Rockefeller University, New York, New York
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Ponsoda X, Jover R, Gómez-Lechón M, Fabra R, Trullenque R, Castell J. The effects of buprenorphine on the metabolism of human hepatocytes. Toxicol In Vitro 1991; 5:219-24. [DOI: 10.1016/0887-2333(91)90021-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/1990] [Revised: 09/24/1990] [Indexed: 11/27/2022]
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Haverkos HW. Infectious diseases and drug abuse. Prevention and treatment in the drug abuse treatment system. J Subst Abuse Treat 1991; 8:269-75. [PMID: 1787552 DOI: 10.1016/0740-5472(91)90050-k] [Citation(s) in RCA: 30] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Several communicable infectious diseases, including AIDS, hepatitis B infection, gonorrhea, syphilis, and tuberculosis, are increasing among drug abusers. Drug abuse treatment programs may be ideal sites to identify those infections and initiate and maintain appropriate medical management. This paper reviews the epidemiology of those infections among drug abusers in the USA, presents rudimentary aspects of medical management of selected infectious diseases, and discusses the need to integrate infectious diseases, drug abuse treatment, and public health approaches if we are to reverse, or at least stabilize, the trends of those diseases.
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Affiliation(s)
- H W Haverkos
- Division of Clinical Research, National Institute on Drug Abuse, United States Public Health Service, Rockville, Maryland 20857
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Lange WR, Fudala PJ, Dax EM, Johnson RE. Safety and side-effects of buprenorphine in the clinical management of heroin addiction. Drug Alcohol Depend 1990; 26:19-28. [PMID: 2209411 DOI: 10.1016/0376-8716(90)90078-s] [Citation(s) in RCA: 67] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Sublingual buprenorphine (8 mg) was administered to heroin-dependent addicts daily for 18 days and continued from day 19-day 36 either daily or on alternate days. Final data are reported on 18 subjects. The number of self-reported symptoms reviewed as potential adverse drug reactions ranged from 1 to 88 per participant. None was considered to be related definitely to the study medication, and there were no reporting differences between the two dosing regimens. Forty-five reactions were considered probably related to buprenorphine: sedation/drowsiness (three reports) and constipation (42 reports). It was concluded that these were anticipated drug effects rather than adverse reactions. Although some participants showed increases in serum aminotransferase levels, those increases could not be directly attributed to buprenorphine. We conclude that buprenorphine was well tolerated, but further study is needed in this population to delineate the possible attributable risk of the drug to hepatic dysfunction in this population.
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Affiliation(s)
- W R Lange
- Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224
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44
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Affiliation(s)
- M D Stein
- Division of General Internal Medicine, Brown University, Rhode Island Hospital, Providence 02903
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45
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Abstract
The liver manufactures albumin at a massive rate and decreases production in times of environmental, nutritional, toxic and trauma stress. Osmotic pressure is a basic evolutionary regulatory factor, and hormonal control over albumin production has been demonstrated. Where and why new or old albumin is degraded are questions which have not been clarified, although the vascular endothelium may well be the degradative site. Albumin is important as a transport protein, as a measure of evolution and as a model to study secretion following synthesis without the intervening steps of glycosylation. Investigations as to how this protein enters the endoplasmic membrane may well answer some of the questions concerning signal peptide insertion (288). The role of the urea cycle intermediate ornithine and its participation in polyamine synthesis, which has a positive effect on albumin synthesis, is under study. Likewise, the inverse relation between acute-phase protein synthesis and albumin synthesis regulated by interleukin 1 and other cytokines will merit further study. These are a few of the concepts which will be tested in the future.
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Affiliation(s)
- M A Rothschild
- Nuclear Medicine Service, Veterans Administration Medical Center, New York, New York 10010
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46
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47
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Zolla-Pazner S, Des Jarlais DC, Friedman SR, Spira TJ, Marmor M, Holzman R, Mildvan D, Yancovitz S, Mathur-Wagh U, Garber J. Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease. Proc Natl Acad Sci U S A 1987; 84:5404-8. [PMID: 3496603 PMCID: PMC298864 DOI: 10.1073/pnas.84.15.5404] [Citation(s) in RCA: 56] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.
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48
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Novick DM, Stenger RJ, Gelb AM, Most J, Yancovitz SR, Kreek MJ. Chronic liver disease in abusers of alcohol and parenteral drugs: a report of 204 consecutive biopsy-proven cases. Alcohol Clin Exp Res 1986; 10:500-5. [PMID: 3541673 DOI: 10.1111/j.1530-0277.1986.tb05131.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
We studied a consecutive series of 204 patients who were admitted to a hospital for addictive diseases during 40 months and who had a liver biopsy. Parenteral drug abusers (n = 34) were significantly younger than alcohol abusers (n = 23) or abusers of both (n = 147) and had lower levels of serum alkaline phosphatase, total bilirubin, and aspartate aminotransferase than the other two groups. Chronic active hepatitis and chronic persistent hepatitis were more frequent (p less than 0.001) in abusers of parenteral drugs alone, whereas cirrhosis was found most often (p less than 0.001) in abusers of both alcohol and parenteral drugs. Cirrhosis was present in 10 of 39 (26%) simultaneous abusers of alcohol and parenteral drugs compared with 58 of 96 (60%) alcohol-abusing former parenteral drug abusers (p less than 0.001). Methadone maintenance treatment was not associated with cirrhosis. Thus, methadone-maintained patients who abuse alcohol and develop cirrhosis should remain in methadone maintenance treatment and receive concomitant alcoholism treatment. Also, these data further support the hypothesis that abusers of both alcohol and parenteral drugs have an increased risk of developing cirrhosis.
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49
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McGuire EJ, DiFonzo CJ, Martin RA, de la Iglesia FA. Evaluation of chronic toxicity and carcinogenesis in rodents with the synthetic analgesic, tilidine fumarate. Toxicology 1986; 39:149-63. [PMID: 3705081 DOI: 10.1016/0300-483x(86)90132-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The carcinogenic potential of tilidine fumarate, a synthetic analgesic, was studied for 80 and 104 weeks in mice and rats, respectively. Groups of 50 albino CF1 mice and 65 albino Wistar rats of each sex received tilidine fumarate-lactose blend (1:1) at doses of 100, 40 and 16 mg/kg. The control groups consisted of 100 mice and 115 rats of each sex and received the lactose vehicle only. Treatment-related non-neoplastic changes consisted of reversible, increased cytoplasmic eosinophilia of hepatocytes in high and mid dose rats corresponding to areas of proliferating smooth endoplasmic reticulum; and an increased incidence in high dose rats of proliferative or cystic lesions of the biliary epithelium. Adequate survival rates allowed stringent statistical analysis of neoplasia. Tilidine did not evoke increased tumor incidences or changes in the average latency or onset of tumors in either species. The most frequent tumors represented spontaneous neoplasia characteristic of historical background incidence in these strains. In mice, the only statistically significant (P less than 0.01) variation in tumor incidence was an increased rate of lung alveologenic adenocarcinomas in females at 100 mg/kg (24%), compared with the concurrent untreated controls (10%), but without a statistically significant difference from historical control data (27%). Female rats given 100 mg/kg showed statistically significant (P less than 0.01) decreased incidences of mammary fibroadenoma and pituitary adenoma. From these data, it was concluded that the synthetic analgesic tilidine does not possess tumorigenic potential in rodents.
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50
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Abstract
Thirty-eight patients maintained on opioid analgesics for non-malignant pain were retrospectively evaluated to determine the indications, course, safety and efficacy of this therapy. Oxycodone was used by 12 patients, methadone by 7, and levorphanol by 5; others were treated with propoxyphene, meperidine, codeine, pentazocine, or some combination of these drugs. Nineteen patients were treated for four or more years at the time of evaluation, while 6 were maintained for more than 7 years. Two-thirds required less than 20 morphine equivalent mg/day and only 4 took more than 40 mg/day. Patients occasionally required escalation of dose and/or hospitalization for exacerbation of pain; doses usually returned to a stable baseline afterward. Twenty-four patients described partial but acceptable or fully adequate relief of pain, while 14 reported inadequate relief. No patient underwent a surgical procedure for pain management while receiving therapy. Few substantial gains in employment or social function could be attributed to the institution of opioid therapy. No toxicity was reported and management became a problem in only 2 patients, both with a history of prior drug abuse. A critical review of patient characteristics, including data from the 16 Personality Factor Questionnaire in 24 patients, the Minnesota Multiphasic Personality Inventory in 23, and detailed psychiatric evaluation in 6, failed to disclose psychological or social variables capable of explaining the success of long-term management. We conclude that opioid maintenance therapy can be a safe, salutary and more humane alternative to the options of surgery or no treatment in those patients with intractable non-malignant pain and no history of drug abuse.
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Affiliation(s)
- Russell K Portenoy
- Pain Service, Department of Neurology, Memorial Sloan-Kettering Cancer Center, and Department of Neurology, Cornell University Medical College, New York, NY 10021 U.S.A
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