RESUMEN
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Cannabis , Alucinógenos , Trastornos Relacionados con Sustancias , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Estudios de Cohortes , Noruega/epidemiologíaRESUMEN
OBJECTIVES: Opioid-use disorder is related to premature death worldwide. Opioid-agonist treatment (OAT) is an effective treatment for opioid dependence. OAT delivery platforms may influence treatment access and outcomes, especially for the most vulnerable groups. The aim of this study was to determine the effectiveness and safety of low-threshold OAT compared to the standard treatment. METHODS: Patients with diagnosed opioid dependence undergoing low-threshold OAT at the Bergen delivery platform in Norway were enrolled in a cohort study in 2014-2019. A national OAT cohort was the reference group. The main outcomes were treatment retention, the use of illicit opioids, non-fatal overdose, overdose death, and all-cause mortality during the first year following treatment initiation and the full treatment period. Additionally, healthcare utilization in the periods before and during OAT was investigated. RESULTS: Compared to the reference cohort, the low-threshold cohort (n = 128, mean age: 38 years, women: 28%) showed treatment retention rates of 95% versus 92%, illicit opioid use of 7% versus 10%, non-fatal overdose of 7% versus 6%, and death at 1.0% versus 1.3%, respectively. The incident rate ratios (IRRs) for healthcare utilization increased substantially during the OAT period compared to the period before; the IRR increased by 3.3 (95% confidence interval (CI): 2.8, 3.9) and 3.4 (95% CI: 3.1, 3.9) for all in- and outpatient healthcare, respectively. CONCLUSIONS: Low-threshold OAT was at least as effective and safe as the standard OAT in terms of treatment retention, the use of illicit opioids, non-fatal overdose, and death. Healthcare utilization increased during the OAT compared to the period before. Lowering the threshold for OAT entrance within proper delivery platforms should be broadly considered to reduce harm and improve healthcare access among patients with opioid dependence.
Asunto(s)
Sobredosis de Droga , Trastornos Relacionados con Opioides , Adulto , Analgésicos Opioides/efectos adversos , Estudios de Cohortes , Sobredosis de Droga/epidemiología , Femenino , Humanos , Masculino , Noruega/epidemiología , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológicoRESUMEN
BACKGROUND: The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. METHODS AND FINDINGS: INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. CONCLUSIONS: Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906.
Asunto(s)
Antivirales/uso terapéutico , Prestación Integrada de Atención de Salud , Consumidores de Drogas , Hepatitis C Crónica/tratamiento farmacológico , Tratamiento de Sustitución de Opiáceos , Abuso de Sustancias por Vía Intravenosa/rehabilitación , Adulto , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Noruega , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/diagnóstico , Respuesta Virológica Sostenida , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. METHODS: Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection. RESULTS: A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2-2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016. CONCLUSION: Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.
Asunto(s)
Analgésicos Opioides/agonistas , Analgésicos Opioides/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Adulto , Analgésicos Opioides/administración & dosificación , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Noruega , Estudios ProspectivosRESUMEN
BACKGROUND: Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017. METHODS: Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models. RESULTS: Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20-23) diazepam equivalents in 2013 to 17 mg (95% CI: 16-17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309-421) in 2013 to 386 mg (95% CI: 349-423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1-3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6-3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs. CONCLUSION: The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Benzodiazepinas/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Gabapentina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Adulto , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: Various integrated care models have been used to improve treatment completion of medications for chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), Mycobacterium tuberculosis (TB), and Human immunodeficiency virus (HIV) among people with substance use disorders (SUD). We have conducted a systematic review to evaluate whether integrated models have impacts of the treatment of infectious diseases among marginalized people with SUD. METHODS: We searched MEDLINE/PubMed (1946 to 2018, on July 26, 2018) and Embase (from 1974 to 2018, on July 26, 2018) for randomized controlled trials (RCTs) and cohort studies evaluating diverse integrated models' effects on sustained virological response (SVR), HIV suppression, HBV curation or suppression, completion of TB treatment regimen among people with SUD. The included studies were assessed qualitatively. RESULTS: Altogether, 1640 studies, and references to 1135 related reviews and RCTs were considered, and only seven RCTs and three cohort studies fulfilled the inclusion criteria. We identified nine integrated care models. Two studies, one RCT and one cohort study, showed a significant effect of their integrated models. The RCT evaluated psychosocial treatment, opioid agonist treatment (OAT) and directly observed TB treatment, and found a significant increase in TB treatment completions among intervention group compared to control group (60% versus 13%, p < 0.01). The cohort study including OAT and TB treatments had an effect on TB treatment completion in hospitalized patients (89% versus 73%, p = 0.03). Eight out of ten studies showed no significant effects of their integrated care models on defined outcomes. One of which having included 363 participants in a RCT showed no effect on SVR compared to the control group when the results adjusted for active substance use and alcohol dependence in a post-hoc analysis (11% versus 7%, p = 0.49). CONCLUSIONS: The findings indicate uncertainty on the effects of integrated care models' on treatment for severe infectious diseases among people with SUD. Some studies point toward that integrated models could improve care of people with SUD, yet high-quality studies and preferably, sufficiently sized clinical trials are needed to conclude on the degree of impact.
Asunto(s)
Enfermedades Transmisibles/diagnóstico , Prestación Integrada de Atención de Salud , Trastornos Relacionados con Sustancias/diagnóstico , Analgésicos Opioides/uso terapéutico , Antituberculosos/uso terapéutico , Enfermedades Transmisibles/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/mortalidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Respuesta Virológica Sostenida , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológicoRESUMEN
BACKGROUND: A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. METHODS: INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. DISCUSSION: This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up. TRIAL REGISTRATION: ClinicalTrials.gov.no. NCT03155906.
Asunto(s)
Antivirales/uso terapéutico , Prestación Integrada de Atención de Salud/métodos , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Tratamiento de Sustitución de Opiáceos , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Cuidados Posteriores , Análisis Costo-Beneficio , Consejo , Femenino , Hepatitis C/etiología , Humanos , Masculino , Noruega , Reacción en Cadena de la Polimerasa , Calidad de Vida , Recurrencia , Abuso de Sustancias por Vía Intravenosa/complicaciones , Respuesta Virológica Sostenida , Cumplimiento y Adherencia al TratamientoRESUMEN
BACKGROUND: A considerable interindividual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6 variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting. METHODS: Information of methadone serum concentration, dose, age, sex, and CYP2C9, CYP2C19, and CYP2D6 genotypes were collected from a routine therapeutic drug monitoring database, whereas variant alleles in CYP2B6 and CYP3A5 were retrospectively genotyped. Linear mixed model analyses were used to study the impact of gene variants on methadone serum concentration/dose (C/D) ratios, including age, sex, and time since the last dose intake as covariates. RESULTS: Overall, 155 serum samples from 62 patients were included in this study. The estimated mean methadone C/D ratios was 17.8 nmol·L·mg for homozygous carriers of CYP2B6*6, which was significantly (P < 0.001) higher than noncarriers (9.2 nmol·L·mg). There was no difference in C/D ratios between heterozygous carriers of CYP2B6*6 (9.1 nmol·L·mg) and noncarriers. An increase in mean methadone C/D ratios was also seen for homozygous carriers of CYP3A5*3 and heterozygous carriers of CYP2C9*2 or *3 and CYP2C19*2 or *3. CONCLUSIONS: Patients homozygous for CYP2B6*6 had a >90% higher methadone C/D ratio. Genotyping of CYP2B6 may therefore be of value when assessing dose requirements in methadone maintenance treatment.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Citocromo P-450 CYP2B6/genética , Metadona/sangre , Metadona/uso terapéutico , Adulto , Alelos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP3A/genética , Monitoreo de Drogas/métodos , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Trastornos Relacionados con Opioides/sangre , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/genética , Polimorfismo Genético/genética , Estudios RetrospectivosRESUMEN
People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Distrés Psicológico , Trastornos Relacionados con Sustancias , Humanos , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
BACKGROUND: A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. OBJECTIVES: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings. METHODS: We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. FINDINGS: A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. CONCLUSIONS: This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes.
Asunto(s)
Metadona , Trastornos Relacionados con Opioides , Humanos , Femenino , Metadona/uso terapéutico , Analgésicos Opioides , Estudios Retrospectivos , Estudios Prospectivos , Sistema Enzimático del Citocromo P-450/genética , Cirrosis Hepática/tratamiento farmacológico , Citocromo P-450 CYP2B6/genéticaRESUMEN
BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.
Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Antivirales , Tratamiento de Sustitución de Opiáceos , Hepatitis C/complicaciones , Fatiga , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
BACKGROUND: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. OBJECTIVES: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. METHODS: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. RESULTS: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810). CONCLUSIONS: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.
Asunto(s)
Metadona , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Metadona/sangre , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/genéticaRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be the second most frequent cause of adverse drug reactions, including drug hypersensitivity, after beta-lactam antibiotics. An understanding of the underlying mechanisms and clinical characteristics of hypersensitivity reactions to NSAIDs is necessary for the diagnosis and management of these undesirable reactions in the clinical setting.
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Antiinflamatorios no Esteroideos/efectos adversos , Hipersensibilidad a las Drogas/etiología , Antiinflamatorios no Esteroideos/inmunología , Antiinflamatorios no Esteroideos/metabolismo , Pruebas de Provocación Bronquial , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/metabolismo , Hipersensibilidad a las Drogas/terapia , Humanos , Pruebas de Provocación Nasal , Pruebas CutáneasRESUMEN
The COVID-19 pandemic has significantly affected treatment services for people with substance use disorders (SUDs). Based on the perspectives of service providers from eight countries, we discuss the impact of the pandemic on SUD treatment services. Although many countries quickly adapted in provision of harm reduction services by changes in policy and service delivery, some went into a forced abstinence-based strategy. Similarly, disruption of abstinence-based approaches such as therapeutic communities has been reported. Global awareness is crucial for responsible management of SUDs during the pandemic, and the development of international health policy guidelines is an urgent need in this area.
RESUMEN
BACKGROUND: Drug hypersensitivity reactions (DHRs) represent an important public health problem. Knowledge of their clinical characteristics will provide improved diagnostic approaches to this topic. OBJECTIVES: The aim of the present study was to describe the clinical characteristics of patients with suspected DHRs. METHODS: The medical records of 206 outpatients with suspected DHRs, who consulted a Norwegian allergy centre from January 2005 to December 2009, were investigated in a retrospective study. RESULTS: Mean age (range) was 44.3 (11-84) years, and 72% of the patients were women. The most common underlying diseases justifying the use of drugs were infections (49%) and pain-related diseases (23%). Antibiotics (53%), non-steroidal anti-inflammatory drugs (NSAIDs) (32%), paracetamol (15%) and other drugs (46%), used as monotherapy or combinations, were the most often suspected drugs. Cutaneous symptoms were the most frequently reported symptoms (83%). Hospitalisation or prolonged hospitalisation was needed in 38% of the cases, and anaphylaxis was reported in 28% of all the patients. Skin prick tests were performed in 185 patients, of which 14 patients had positive test results. Drug provocation tests (DPTs) were performed in only 86 patients, six of which had positive reactions. DHRs were confirmed in 24 and rejected in 81 patients. Unsettled cases (39%) were mainly due to not performing DPTs. CONCLUSIONS: Suspected DHRs occur predominantly in women. The most common manifestations are cutaneous symptoms, but life-threatening reactions justifying hospitalisation may occur. Antibiotics and NSAIDs are the two drug families most frequently suspected. DPTs need to be included in diagnostic protocols in order to evaluate suspected DHRs.
Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Revisión de la Utilización de Medicamentos/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Noruega , Estudios Retrospectivos , Pruebas Cutáneas , Adulto JovenRESUMEN
BACKGROUND: Continuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, injecting substance use, age, and gender on substance use over time among patients undergoing outpatient SUD treatment. METHODS: We used data from a cohort of SUD patients in Norway obtained from health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including substances and frequency of use, were assessed for 708 SUD patients in 2016-2020. Of those, 171 patients provided two or more substance use measurements. The total substance use was calculated, creating a substance use severity index (SUSI), ranging from zero (no use) to one (daily use of all substances). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze the SUSI at baseline and over time, and its associations with inpatient detoxification, injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI). RESULTS: No longitudinal changes in the SUSI were found compared with baseline (change in SUSI (cSUSI): 0.04, 95% CI: - 0.05;0.13, p = 0.397). Likewise, "inpatient detoxification" was not associated with changes in the SUSI compared with "no inpatient detoxification" (cSUSI: 0.00, 95% CI: - 0.04;0.04, p = 0.952). However, injecting substances were associated with a higher SUSI than not injecting substances at baseline (difference in SUSI: 0.19, 95% CI: 0.16;0.21, p = < 0.001), and starting to inject substances was associated with increasing SUSI over time compared with not starting to inject substances (cSUSI: 0.11, 95% CI: 0.07;0.15, p = < 0.001). Gender was not significantly associated with changes in the SUSI (cSUSI: - 0.04, 95% CI: - 0.07;0.00, p = 0.052), while patients over 60 years of age had a lower SUSI than those under the age of 30 at baseline (difference in SUSI: - 0.08, 95% CI: - 0.14;- 0.01, p = 0.018), with no change over time (cSUSI: - 0.05, 95% CI: - 0.16;0.05, p = 0.297). CONCLUSION: The present study demonstrates that inpatient detoxification was not associated with substance use changes over time for patients undergoing outpatient SUD treatment. Otherwise, injecting substance use was a particular risk factor for a high level of substance use. Future research needs to evaluate the impact of other treatment approaches on substance use, ideally in randomized controlled trials.
Asunto(s)
Sobredosis de Droga , Trastornos Relacionados con Sustancias , Anciano , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Prospectivos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapiaRESUMEN
BACKGROUND: There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments. METHODS: This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data. RESULTS: The mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049). CONCLUSIONS: The findings suggest that the patient's self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.
Asunto(s)
Metadona , Trastornos Relacionados con Opioides , Animales , Estudios de Cohortes , Femenino , Humanos , Metadona/efectos adversos , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Estudios Prospectivos , PorcinosRESUMEN
BACKGROUND: There are few longitudinal follow-up studies of patients in opioid maintenance treatment (OMT). For this reason we performed a follow-up study of a cohort of 67 women who had used OMT-medications during pregnancy an average of ten years earlier. The aim of our study was to explore how the women were doing over time regarding OMT medication adherence and use of other legal and illegal substances, as well as to evaluate the mortality for the women and custody situation for the children in the cohort. METHODS: Participants were recruited from two cohorts in our previous pregnancy study covering women who gave birth from 2004 to 2009. Sixty-seven women agreed to be interviewed, which is 73% of the eligible women from our original study. We developed a questionnaire, which we used in the interview, that focused primarily on these women's current life situation (custody of child they had delivered, the use of medications in OMT and other legal and illegal substances, and several other health and social aspects of the participants' lives). RESULTS: Two women had died prior to the follow-up. Eighty-one percent of the women had custody of the child they had delivered in our pregnancy study and half the women were single parents. Fifty-four percent of the women were employed. At follow-up, 42% of the women were in methadone maintenance treatment (MMT), 39% were in buprenorphine maintenance treatment (BMT), and 19% had left OMT. One-third of the women had changed their OMT medication during the follow-up period. The majority (77%) were satisfied with their current OMT medication. The women in MMT seemed to be more severe substance dependent than the rest of the participants. There was little use of legal and illegal substances at follow-up, especially among women with custody of their child. The frequency of substance use was low. Fourteen percent of the women were in the process of leaving OMT and another half of the women wanted to leave OMT, but had no plan for how and when. CONCLUSION: This follow-up study describes a predominantly well rehabilitated cohort of women who had given birth while in OMT ten years earlier. The majority of the women had custody of their children and used very few legal and illegal drugs. Our findings may be explained partly from a life course perspective, with the women having experienced turning points when starting OMT or becoming mothers.
Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Buprenorfina/uso terapéutico , Niño , Femenino , Estudios de Seguimiento , Humanos , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , EmbarazoRESUMEN
BACKGROUND: The impact of clinical and sociodemographic factors on fatigue remains unknown among patients with substance use disorders (SUD). This study aims to evaluate fatigue among patients with SUD using a nine-item fatigue severity scale (FSS-9) and identify the impact that clinical and sociodemographic factors - such as injecting substance use, chronic infectious diseases, liver fibrosis, opioid agonist therapy (OAT), debt difficulties, and housing situation - have on fatigue. METHODS: We used data from a cohort of patients with SUD in Norway with annual health assessments surveying FSS-9 and some clinical and sociodemographic factors. A total of 915 FSS-9 measurements were collected from 654 patients during the period 2016-2020. We defined baseline as the first annual health assessment when the health assessments were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyse whether the clinical and sociodemographic factors affected the FSS-9 sum score, presented with beta coefficients (ß) with 95% confidence intervals (CI). RESULTS: The mean sum score of the FSS-9 was 43 (standard deviation: 16) at baseline. Females compared with males (adjusted mean difference of FSS-9 sum score: 4.1, 95% CI: 1.3-7.0), having debt difficulties compared with having no debt difficulties (2.9;0.4-5.3), and frequent use of benzodiazepines (5.7;3.0-8.4) or amphetamines (-5.0;-8.0- -2.0) compared to less frequent or no use of these substances changed the FSS-9 baseline sum score. The other clinical and sociodemographic factors did not predict any clinically relevant change in the FSS-9 sum score from baseline to the following health assessments. CONCLUSION: Patients with SUD suffer from high levels of fatigue. Female patients, patients with debt difficulties, and those with extensive use of benzodiazepines are at particular risk of being fatigued. This should be taken into consideration when planning health services.
Asunto(s)
Fatiga/epidemiología , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Enfermedades Transmisibles/epidemiología , Femenino , Estado de Salud , Humanos , Cirrosis Hepática/epidemiología , Masculino , Salud Mental , Persona de Mediana Edad , Noruega , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. METHODS: This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. RESULTS: In total 3529 individuals were identified with dispensed OAT in the Swedish cohort and 7739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). CONCLUSIONS: An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.