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3.
Biol Psychiatry ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32305216

RESUMO

BACKGROUND: Maintenance treatment with opioid agonists (buprenorphine, methadone) is effective for opioid addiction but does not eliminate opioid use in all patients. We modeled maintenance treatment in rats that self-administered the prescription opioid oxycodone. The maintenance medication was either buprenorphine or the G protein-biased mu opioid receptor agonist TRV130. We then tested prevention of oxycodone seeking and taking during abstinence using a modified context-induced reinstatement procedure, a rat relapse model. METHODS: We trained rats to self-administer oxycodone (6 hours/day, 14 days) in context A; infusions were paired with discrete tone-light cues. We then implanted osmotic pumps containing buprenorphine or TRV130 (0, 3, 6, or 9 mg/kg/day) and performed 3 consecutive tests: lever pressing reinforced by oxycodone-associated discrete cues in nondrug context B (extinction responding), context-induced reinstatement of oxycodone seeking in context A, and reacquisition of oxycodone self-administration in context A. We also tested whether TRV130 maintenance would protect against acute oxycodone-induced decreases in nucleus accumbens oxygen levels. RESULTS: In male rats, buprenorphine and TRV130 decreased extinction responding and reacquisition of oxycodone self-administration but had a weaker (nonsignificant) effect on context-induced reinstatement. In female rats, buprenorphine decreased responding in all 3 tests, while TRV130 decreased only extinction responding. In both sexes, TRV130 prevented acute brain hypoxia induced by moderate doses of oxycodone. CONCLUSIONS: TRV130 decreased oxycodone seeking and taking during abstinence in a partly sex-specific manner and prevented acute oxycodone-induced brain hypoxia. We propose that G protein-biased mu opioid receptor agonists, currently in development as analgesics, should be considered as relapse prevention maintenance treatment for opioid addiction.

4.
Med Image Anal ; 63: 101696, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32330851

RESUMO

Classification of various types of tissue in cancer histology images based on the cellular compositions is an important step towards the development of computational pathology tools for systematic digital profiling of the spatial tumor microenvironment. Most existing methods for tissue phenotyping are limited to the classification of tumor and stroma and require large amount of annotated histology images which are often not available. In the current work, we pose the problem of identifying distinct tissue phenotypes as finding communities in cellular graphs or networks. First, we train a deep neural network for cell detection and classification into five distinct cellular components. Considering the detected nuclei as nodes, potential cell-cell connections are assigned using Delaunay triangulation resulting in a cell-level graph. Based on this cell graph, a feature vector capturing potential cell-cell connection of different types of cells is computed. These feature vectors are used to construct a patch-level graph based on chi-square distance. We map patch-level nodes to the geometric space by representing each node as a vector of geodesic distances from other nodes in the network and iteratively drifting the patch nodes in the direction of positive density gradients towards maximum density regions. The proposed algorithm is evaluated on a publicly available dataset and another new large-scale dataset consisting of 280K patches of seven tissue phenotypes. The estimated communities have significant biological meanings as verified by the expert pathologists. A comparison with current state-of-the-art methods reveals significant performance improvement in tissue phenotyping.

5.
Gac. sanit. (Barc., Ed. impr.) ; 34(2): 133-140, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS-Express | ID: ibc-ET1-5700

RESUMO

OBJECTIVE: To compare the use of health technology assessment (HTA) as a tool to support pricing and reimbursement (P&R) of new medicines in Spain with England, Sweden, France and Germany. METHOD: For each country, the literature is used to identify the purpose and timing of the P&R decision, the HTA and decision-making procedures used to generate evidence, and the criteria used to make decisions. RESULTS: Results are presented as a summary of the HTA landscape for P&R of new medicines in each country.comparisons are made between Spain and other countries regarding the procedure and implementation of HTA. CONCLUSIONS: Based on these assessments, we made recommendations for how HTA might develop in Spain with the aim of improving governance and efficiency. Spain has made considerable progress in recent years, but still falls short of international standards in terms of independence of the HTA agencies and decision-making committees from political influence and industrial policy, the setting of prices of medicines in relation to health gain, improve the transparency of the process and results of the evaluation, and promote the participation of stakeholders. In common with other countries, Spain needs to clarify the role of cost-effectiveness criteria. Further progress needs to be made to coordinate effort across the various agencies, strengthen technical staff, and ensure equitable access to medicines between regions


OBJETIVO: Comparar el uso de la evaluación de tecnologías sanitarias (ETS) como instrumento para apoyar la fijación de precios y el reembolso de nuevos medicamentos en España con otros países europeos como Inglaterra, Suecia, Francia y Alemania. MÉTODO: Se realiza una revisión de la literatura para identificar, en cada país, el objetivo y la cronología de la decisión, los procedimientos para realizar la ETS y los criterios para tomar decisiones. RESULTADOS: Se presenta una descripción narrativa de la situación en cada país y una comparación entre España y otros países sobre los procedimientos y la implementación de ETS. CONCLUSIONES: Basándose en estas evaluaciones, se propone una serie de recomendaciones para mejorar el proceso. España ha avanzado significativamente en ETS en los últimos años, pero aún falta garantizar la independencia de las agencias de ETS, eliminar la influencia de la política económica e industrial de los comités de decisiones sanitarias, fijar precios basados en el valor terapéutico, mejorar la transparencia del proceso y de los resultados de las evaluaciones, y por último, aumentar la participación de los grupos de interés. Al igual que en otros países de su entorno, España tiene que clarificar el papel de la evaluación económica como criterio de decisión. Hace falta una mejor coordinación entre las diversas agencias que participan en ETS en España, fomentar el personal técnico y monitorizar la equidad de acceso a nuevos medicamentos entre las comunidades autónomas

8.
Eur J Health Econ ; 21(4): 529-542, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31960181

RESUMO

According to the most traditional economic evaluation manuals, all "relevant" costs should be included in the economic analysis, taking into account factors such as the patient population, setting, location, year, perspective and time horizon. However, cost information may be designed for other purposes. Health care organisations may lack sophisticated accounting systems and consequently, health economists may be unfamiliar with cost accounting terminology, which may lead to discrepancy in terms used in the economic evaluation literature and management accountancy. This paper identifies new tendencies in costing methodologies in health care and critically comments on each included article. For better clarification of terminology, a pragmatic glossary of terms is proposed. A scoping review of English and Spanish language literature (2005-2018) was conducted to identify new tendencies in costing methodologies in health care. The databases PubMed, Scopus and EconLit were searched. A total of 21 studies were included yielding 43 costing analysis. The most common analysis was top-down micro-costing (49%), followed by top-down gross-costing (37%) and bottom-up micro-costing (14%). Resource data were collected prospectively in 12 top-down studies (32%). Hospital database was the most common way of collection of resource data (44%) in top-down gross-costing studies. In top-down micro-costing studies, the most resource use data collection was the combination of several methods (38%). In general, substantial inconsistencies in the costing methods were found. The convergence of top-down and bottom-up methods may be an important topic in the next decades.

9.
Value Health ; 23(1): 25-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31952669

RESUMO

BACKGROUND: The economic evaluation of healthcare technologies has become in many countries a basic tool for reimbursement, pricing and purchasing decisions. OBJECTIVE: The objective of this article is to examine the institutional, legal, and political factors that have impeded the application of economic evaluation and the criterion of efficiency in the process of pricing and reimbursement of new medicines in Spain. METHODS: Narrative description of the current institutional framework for the use of economic evaluation in pricing and reimbursement in Spain, legal and policy framework in the field of evaluation of new medicines, and stakeholder initiatives and policies related to the use of economic evaluation outside of the pricing and reimbursement process. RESULTS: Spain has an institutional framework created and established over the last years that could have facilitated a formal use of economic evaluation in the process of pricing and reimbursement. Nevertheless, the real use of economic evaluation at the central or regional level is still unknown, although application of the efficiency criterion, linking to cost-effectiveness, has been clearly required by Spanish laws and regulations at the national level. We highlight a certain degree of moral hazard from the central government that is not directly responsible for the budget impact of reimbursement and pricing decisions. There are currently a number of ongoing initiatives in the field of economic evaluation by various agents, but they remain uncoordinated. CONCLUSIONS: Poor governance at the highest level of decision making is the main reason for the lack of interest in economic evaluation. A profound political change, supported by transparency and accountability, is required before the criterion of efficiency can be fully considered in the process of pricing and reimbursement of new medicines in Spain.

10.
Drug Alcohol Depend ; 207: 107698, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816489

RESUMO

BACKGROUND: Sleep disturbance is common in patients with opioid use disorder (OUD) receiving medication for addiction treatment. Differences between patients on the two primary agonist medications-methadone and buprenorphine-are not well understood. METHODS: In patients receiving either methadone or buprenorphine treatment for OUD, we examined sleep continuity and architecture using ambulatory monitoring to gather both an objective measure (daily sleep EEG; M = 5.76 days, SD = 1.46) and a subjective measure (daily sleep diary; M = 54.10 days, SD = 25.10) of sleep. RESULTS: Patients treated with buprenorphine versus methadone did not differ on any measure of sleep continuity or architecture. Women had longer EEG-derived total sleep time than men (d = -0.68, 95 % CI -1.32 to -0.09), along with lower %N2 (d = 0.94, 95 % CI 0.34-1.64) and greater %N3 (d = -0.94, 95 % CI -1.61 to -0.32). Self-reported sleep differed from EEG-derived estimates: wake after sleep onset was greater by EEG than by diary (d = 2.58, 95 % CI 1.74-3.63), and total sleep time and sleep efficiency were lower by EEG than by diary (d for sleep time = 2.93, 95 % CI 2.06-4.14; d for efficiency = 1.69, 95 % CI 0.98-2.49). CONCLUSIONS: Patients treated with buprenorphine or methadone did not substantively differ in ambulatory measures of sleep. With both medications, there was a discrepancy between objective and subjective sleep measures. Further confirmatory evidence would inform the development of sleep-related recommendations for OUD patients undergoing agonist treatment.

12.
Gac. sanit. (Barc., Ed. impr.) ; 33(6): 529-535, nov.-dic. 2019. tab, graf
Artigo em Inglês | IBECS-Express | ID: ibc-ET1-4641

RESUMO

OBJECTIVE: Adequate physical activity levels and a healthy lifestyle may prevent all kinds of non-communicable diseases, promote well-being and reduce health-care costs among perimenopausal women. This study assessed an exercise programme for perimenopausal women. METHOD: A total of 150 women (aged 45-64 years) not engaged in regular physical activity were randomly assigned to either a 16 week exercise intervention or to the control group. The study was conducted from the perspective of the National Health System. Health outcomes were quality-adjusted life years (QALYs), measured by the EuroQol-5D-5L questionnaire. The total direct costs of the programme were the costs of visits to primary care, specialty care, emergency, medicines, instructor cost and infrastructure cost. The results were expressed as the incremental cost-effectiveness ratio. Sensitivity analysis was undertaken to test the robustness of the analysis. RESULTS: Mean QALYs over 16 weeks were.228 in the control group and.230 in the intervention group (mean difference: .002; 95% confidence interval [95%CI]: -0.005 to 0.009). Improvements from baseline were greater in the intervention group in all dimensions of the EuroQol-5D-5L but not statistically significant. The total costs at the end of the intervention were 160.38 € in the control group and 167.80 € in the intervention group (mean difference: 7.42 €; 95%CI: -47 to 62). The exercise programme had an incremental cost-effectiveness ratio of 4,686 €/QALY. CONCLUSIONS: The programme could be considered cost-effective, although the overall difference in health benefits and costs was very modest. Longer term follow-up is needed


OBJETIVO: El ejercicio físico puede promover el bienestar y reducir los costes de atención médica en las mujeres perimenopáusicas. Este estudio evalúa un programa de ejercicio físico en mujeres perimenopáusicas. MÉTODO: Un total de 150 mujeres (de edades comprendidas entre 45 y 64 años) fueron asignadas aleatoriamente al grupo de intervención o al grupo de control. El estudio ha tenido una duración de 16 semanas. Los resultados en salud se han medido en años de vida ajustados por calidad (AVAC) mediante el cuestionario EuroQol-5D-5L. Se ha considerado el total de costes directos del programa, integrado por los costes de las visitas en atención primaria, atención especializada y urgencias, medicamentos, coste del monitor y coste de las instalaciones. Los resultados se han expresado como ratio coste-efectividad incremental. La robustez del modelo se ha contrastado con un análisis de sensibilidad. RESULTADOS: Al final de la intervención, los AVAC fueron 0,228 en el grupo de control y 0,230 en el grupo de intervención (diferencia media: 0,002; intervalo de confianza del 95% [IC95%]: -0,005 a 0,009). La mejoría fue mayor en el grupo de intervención en todas las dimensiones del EuroQol-5D-5L, pero sin significación estadística. Los costes totales al finalizar la intervención han sido de 160,38 € en el grupo de control y 167,80 € en el de intervención (diferencia media: 7,42 €; IC95%: -47 a 62). El programa de ejercicio físico ha tenido una ratio coste-efectividad incremental de 4686 €/AVAC. CONCLUSIÓN: El programa debe considerarse coste-efectivo, aunque la diferencia en resultados de salud y costes ha sido muy moderada. Se necesita un seguimiento a más largo plazo

13.
Am J Psychiatry ; 176(11): 888-891, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672042
14.
Blood Adv ; 3(22): 3602-3612, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31743391

RESUMO

Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.

15.
Gac Sanit ; 2019 Nov 24.
Artigo em Espanhol | MEDLINE | ID: mdl-31776044

RESUMO

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria.

16.
Ann Surg ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31592810

RESUMO

BACKGROUND: EVAR for abdominal aortic aneurysm has an initial survival advantage over OR, but more frequent complications increase costs and long-term aneurysm-related mortality. Randomized controlled trials of EVAR versus OR have shown EVAR is not cost-effective over a patient's lifetime. However, in the EVAR-1 trial, postoperative surveillance may have been sub-optimal, as the importance of sac growth as a predictor of graft failure was overlooked. METHODS: Real-world data informed a discrete event simulation model of postoperative outcomes following EVAR. Outcomes observed EVAR-1 were compared with those from 5 alternative postoperative surveillance and re-intervention strategies. Key events, quality-adjusted life years and costs were predicted. The impact of using complication and rupture rates from more recent devices, imaging and re-intervention methods was also explored. RESULTS: Compared with observed EVAR-1 outcomes, modeling full adherence to the EVAR-1 scan protocol reduced abdominal aortic aneurysm (AAA) deaths by 3% and increased elective re-interventions by 44%. European Society re-intervention guidelines provided the most clinically effective strategy, with an 8% reduction in AAA deaths, but a 52% increase in elective re-interventions. The cheapest and most cost-effective strategy used lifetime annual ultrasound in primary care with confirmatory computed tomography if necessary, and reduced AAA-related deaths by 5%. Using contemporary rates for complications and rupture did not alter these conclusions. CONCLUSIONS: All alternative strategies improved clinical benefits compared with the EVAR-1 trial. Further work is needed regarding the cost and accuracy of primary care ultrasound, and the potential impact of these strategies in the comparison with OR.

17.
J Cancer ; 10(21): 5130-5138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602266

RESUMO

Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.

18.
Gac. sanit. (Barc., Ed. impr.) ; 33(5): 442-449, sept.-oct. 2019. tab, graf
Artigo em Espanhol | IBECS-Express | ID: ibc-ET1-4466

RESUMO

Objetivo: Este estudio examina la elección individual de seguro sanitario privado en España. La elección del seguro privado revela los atributos del sistema sanitario que son más valorados por la población, así como la capacidad de respuesta de este en relación a esas preferencias. Método: Los datos proceden de las oleadas de 2004, 2009 y 2014 del Barómetro Sanitario, examinando de forma separada la elección de la población general y de los funcionarios públicos. Resultados: El sistema sanitario público tenía una valoración muy buena en atributos como tecnología y capacitación de los médicos, incluso por aquellos que eligieron un seguro privado, pero no tanto en características como la comodidad o la rapidez de respuesta. Sin embargo, nuestro estudio muestra que los individuos se preocupan por otros atributos del sistema sanitario relacionados con la capacidad de respuesta, como el trato personal y la información, y estos influyen en su decisión de contratar un seguro privado. El cuerpo de funcionarios, incluso la minoría que ha optado por la sanidad pública, tiene una percepción más crítica sobre la sanidad pública que los no funcionarios, especialmente en trato personal, información, atención primaria y especialistas. Conclusiones: Las fortalezas y debilidades sobre el desempeño del sistema público de salud encontradas en este estudio serán de interés para los formuladores de políticas sanitarias y merecen una mayor investigación


Objective: This study examines individuals' choice of private health insurance in Spain. Private health insurance choices reveal the attributes of health care most highly valued by the population, and the perceived responsiveness of the public system in delivering those preferences. Method: The paper exploits the 2004, 2009 and 2014 waves of the national Health Barometer survey, examining the health insurance choice separately for the general population and a small but influential sector of elite public-sector employees who can opt out from the public health system (civil servants). Results: Public healthcare is a highly regarded provider in terms of technology and doctor training, even by those who chose private health insurance, but falls short in terms of amenities such as comfort and speed of attendance. These findings confirm well-known strengths and criticisms of the public system. However, the study also finds that citizens are concerned about the performance of the public sector in key domains of health system responsiveness, such as personal contact and information and these concerns also influence their decision to opt for private provision. Finally, civil servants, even the minority who opted for public provision, tend to have a lower opinion of the public health service than non-civil servants, especially in terms of personal contact, information, primary care and specialist care. Conclusions: These perceptions and concerns of the public about the performance of the public health service will be of interest for policy makers and should be investigated further

19.
Gac Sanit ; 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31530485

RESUMO

OBJECTIVE: In this study we conducted an economic evaluation of a surveillance programme to prevent hip dislocation in children with cerebral palsy. METHOD: We developed a model that compared costs and health outcomes of children with cerebral palsy with and without a surveillance programme. Information from a number of sources was combined into a decision analytical model, primarily based on data from a comparative study with a 20-year follow-up. Effectiveness was measured using Quality-Adjusted Life Years (QALYs). The analysis took the perspective of the Spanish National Health Service. We undertook extensive sensitivity analyses including a probabilistic sensitivity analysis. RESULTS: The surveillance programme led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of 12,282€. The results were robust to model assumptions. The probability that the programme was cost-effective was estimated to be over 80% at the threshold of 25.000€/QALY recommended in Spain. CONCLUSION: This study indicates that surveillance programmes to prevent hip dislocation in children with cerebral palsy are likely to be cost-effective.

20.
J Subst Abuse Treat ; 106: 43-57, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31540611

RESUMO

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00-09:00) vs. Late hours (12:00-13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00-11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

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