| 1. |
- Cho, Jeong-woo, 1978-, et al.
(författare)
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Dynamic Buffer Management Scheme Based on Rate Estimation in Packet-Switched Networks
- 2002
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Ingår i: Computer Networks. - : Elsevier. - 1389-1286 .- 1872-7069. ; 39:6, s. 769-787
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Tidskriftsartikel (refereegranskat)abstract
- While traffic volume of real-time applications is rapidly increasing, current routers do not guarantee minimum QoS values of fairness and drop packets in random fashion. If routers provide a minimum QoS, resulting less delays, more fairness, and smoother sending rates, TCP-friendly rate control (TFRC) can be adopted for real-time applications. We propose a dynamic buffer management scheme that meets the requirements described above, and can be applied to TCP flow and to data flow for transfer of real-time applications. The proposed scheme consists of a virtual threshold function, an accurate and stable per-flow rate estimation, a per-flow exponential drop probability, and a dropping strategy that guarantees fairness when there are many flows. Moreover, we introduce a practical definition of active flows to reduce the overhead coming from maintaining per-flow states. We discuss how proposed scheme motivates real-time applications to adopt TFRC.
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| 2. |
- Doerner, K, et al.
(författare)
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high performance computing in the optimization of software test plans
- 2002
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Ingår i: Optimization and Engineering. - 1389-4420 .- 1573-2924. ; 3:1, s. 67-87
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Tidskriftsartikel (refereegranskat)abstract
- Statistical software testing is an increasingly popular method in the software development cycle. An exact modeling of the usage profiles of a software system is an indispensable prerequisite for statistical testing. Recently, new techniques for obtaining optimal usage profiles even the presence of rarely used critical functions have been introduced. Although these techniques deliver unbiased dependability estimates with a single model (instead of using multiple models as it is the current practice) their applicability is hampered by their prohibitive computational complexity.
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| 3. |
- Espvall, Majen, et al.
(författare)
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Social networks of women with undefined musculoskeletal disorder
- 2002
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Ingår i: Social Work in Health Care. - : Taylor & Francis. - 0098-1389 .- 1541-034X. ; 36:1, s. 77-91
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Tidskriftsartikel (refereegranskat)abstract
- This study was conducted to investigate social integration among, and the availability of social support for, female patients with undefined musculoskeletal disorder compared to women with coronary heart disease. The aim was to elucidate the importance of a clear diagnosis for the social network relationships of these female patients. For the measurement of social support two instruments were used: an abbreviated version of the Interview Schedule for Social Interaction and a condensed version of the Interpersonal Support Evaluation List. After adjustment for age, marital and employment status, significant differences can be recognized between the two groups of patients: MSD-patients interact with fewer people and receive less emotional support. Implications for social work practice and issues for future research are presented.
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| 4. |
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| 5. |
- Norlin, Anna, et al.
(författare)
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Investigation of Interfacial Capacitance of Pt, Ti and TiN Coated Electrodes by Electrochemical Impedance Spectroscopy
- 2002
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Ingår i: Biomolecular Engineering. - 1389-0344 .- 1878-559X. ; 19:2-6, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical processes at the electrode-electrolyte (body fluid) interface are of ultimate importance for stimulating/sensing electrode function. A high electrode surface area is desirable for safe stimulation through double-layer charging and discharging. Pt and Pt-Ir alloys have been the most common electrode materials. The use of TiN coating as the surface layer on the electrode has found increasing interest because of its metal-like conductivity, excellent mechanical and chemical properties, and the fact that it can be deposited with a high surface area. In this work, electrochemical impedance spectroscopy (EIS), which is a sensitive and non-destructive technique and widely used for characterization of electrical properties of electrode-electrolyte interfaces, was applied to investigate pure Pt and Ti, and TiN coated electrodes exposed to a phosphate-buffered-saline (PBS) solution. Platinized Pt and Ti were also studied for comparison. The capacitance value of the electrodes in PBS was obtained through quantitative analysis of the EIS spectra. The results reveal that the capacitance of the TiN coated electrodes with a rough surface is several hundreds times higher than that of a smooth Pt surface. Platinization of Ti can also increase the capacitance to the same extent as platina. EIS has been shown to be a powerful technique for characterization of stimulating/sensing electrodes.
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| 6. |
- Caudle, Kelly E, et al.
(författare)
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Incorporation of Pharmacogenomics into Routine Clinical Practice : the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process
- 2014
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 15:2, s. 209-217
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Tidskriftsartikel (refereegranskat)abstract
- The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine's Standards for Developing Trustworthy Clinical Practice Guidelines.
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| 7. |
- Darwich, A. S., et al.
(författare)
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Interplay of Metabolism and Transport in Determining Oral Drug Absorption and Gut Wall Metabolism : A Simulation Assessment Using the "Advanced Dissolution, Absorption, Metabolism (ADAM)" Model
- 2010
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 11:9, s. 716-729
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Forskningsöversikt (refereegranskat)abstract
- Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut wall which may contribute to gut first pass metabolism, Cytochrome P450 (CYP) 3A has been shown to play a major role. The efflux transporter P-glycoprotein (P-gp; MDR1/ABCB1) is the most extensively studied drug efflux transporter in the gut and might have a significant role in the regulation of GI absorption. Although not every CYP3A substrate will have a high extent of gut wall first-pass extraction, being a substrate for the enzyme increases the likelihood of a higher first-pass extraction. Similarly, being a P-gp substrate does not necessarily pose a problem with the gut wall absorption however it may reduce bioavailability in some cases (e. g. when drug has low passive permeability). An on-going debate has focused on the issue of the interplay between CYP3A and P-gp such that high affinity to P-gp increases the exposure of drug to CYP3A through repeated cycling via passive diffusion and active efflux, decreasing the fraction of drug that escapes first pass gut metabolism (F-G). The presence of P-gp in the gut wall and the high affinity of some CYP3A substrates to this transporter are postulated to reduce the potential for saturating the enzymes, thus increasing gut wall first-pass metabolism for compounds which otherwise would have saturated CYP3A. Such inferences are based on assumptions in the modelling of oral drug absorption. These models should be as mechanistic as possible and tractable using available in vitro and in vivo information. We review, through simulation, this subject and examine the interplay between gut wall metabolism and efflux transporters by studying the fraction of dose absorbed into enterocytes (F-a) and F-G via systematic variation of drug characteristics, in accordance with the Biopharmaceutics Classification System (BCS) within one of the most physiological models of oral drug absorption currently available, respectively ADAM. Variables studied included the intrinsic clearance (CLint) and the Michaelis-Menten Constant (K-m) for CYP3A4 and P-gp (CLint-CYP3A4 and Km-CYP3A4, CLint-P-gp and Km-P-gp). The impact of CYP3A4 and P-gp intracellular topography were not investigated since a well-stirred enterocyte is assumed within ADAM. An increased CLint-CYP3A4 resulted in a reduced F-G whereas an increase in CLint-P-gp resulted in a reduced F-a, but interestingly decreased F-G too. The reduction in F-G was limited to certain conditions and was modest. Non-linear relationships between various parameters determining the permeability (e. g. P-app, CLint-P-gp, and Km-P-gp) and gut wall metabolism (e. g. CLint-CYP3A4, Km-CYP3A4) resulted in disproportionate changes in F-G compared to the magnitude of singular effects. The results suggest that P-gp efflux decreases enterocytic drug concentration for drugs given at reasonably high dose which possess adequate passive apparent permeability (high P-app), by de-saturating CYP3A4 in the gut resulting in a lower F-G. However, these findings were observed only in a very limited area of the parameters space matching very few herapeutic drugs (a group with very high metabolism, high turn-over by efflux transporters and low F-a). The systematic approach in this study enabled us to recognise the combination of parameter values where the potential interplay between metabolising enzymes and efflux transporters is expected to be highest, using a realistic range of parameter values taken from an intensive literature search.
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| 8. |
- Korkina, L., et al.
(författare)
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The chemical defensive system in the pathobiology of idiopathic environment-associated diseases
- 2009
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Ingår i: Current drug metabolism. - 1389-2002 .- 1875-5453. ; 10:8, s. 914-931
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Forskningsöversikt (refereegranskat)abstract
- Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic, and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies.
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| 9. |
- Lennernäs, Hans
(författare)
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Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data : experience from in vivo dissolution and permeability studies in humans
- 2007
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Ingår i: Current drug metabolism. - 1389-2002 .- 1875-5453. ; 8:7, s. 645-657
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Forskningsöversikt (refereegranskat)abstract
- The majority (84%) of the 50 most-sold pharmaceutical products in the US and European markets are given orally. The dominating role of this route in drug therapy is a consequence of it being safe, efficient and easily accessible with minimal discomfort to the patient in comparison with other routes of drug administration. A successful drug discovery and development of oral pharmaceutical products require an in-depth understanding of multiple biochemical and physiological processes that determine the dissolution rate, intestinal permeability, gastrointestinal transit, first-pass extraction and systemic exposure-time profiles of drugs. It is crucial to realize that these basic biopharmaceutic and pharmacokinetic properties are crucial to focus on to allow successful drug development. Identification of the rate-limiting step(s) in order to overcome these barriers and understanding of the sources of variability are important in the selection of suitable candidate molecules in drug development. Several reports based on in vitro investigations in various cell models have suggested that carrier-mediated intestinal efflux may be a major reason for incomplete absorption and variable bioavailability of drugs, as well being a site for drug-drug and specific food-drug interactions. However, many drugs which were initially suggested to undergo significant efflux in vitro were later shown to be completely absorbed in vivo. This apparent discrepancy between in vitro and in vivo results may be due to several factors that will be discussed in this review. Novel data on solubility and dissolution in human gastrointestinal derived fluids will be reviewed. The effect of food intake on solubility and dissolution rate of a range of drugs including felodipine, danazol, griseofulvin, cyclosporine, probucol and ubiquinone in simulated and real intestinal fluids is discussed. The biopharmaceutic and physicochemical data discussed here can potentially be used as a benchmark set for validation of new experimental techniques or in silico models in future. Factors such as structural diversity, commercial availability, price and a suitable analytical technique for quantification were considered in the selection of a specific drug set. Using the compiled data set lipophilicity as determined by reverse phase HPLC and permeability across Caco-2 cell monolayers were determined; means to overcome the experimental difficulties due to the diversity of the data are also discussed.
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| 10. |
- Lundell, Kerstin, et al.
(författare)
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Species-specific and age-dependent bile acid composition : Aspects on CYP8B and CYP4A subfamilies in bile acid biosynthesis
- 2008
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 9:4, s. 323-331
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Forskningsöversikt (refereegranskat)abstract
- The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12 alpha or 6 alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12 alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6 alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6 alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.
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| 11. |
- Pisanu, Claudia, et al.
(författare)
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We are not Alone in Our Body : Insights into the Involvement of Microbiota in the Etiopathogenesis and Pharmacology of Mental Illness
- 2018
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Ingår i: Current drug metabolism. - : BENTHAM SCIENCE PUBL LTD. - 1389-2002 .- 1875-5453. ; 19:8, s. 688-694
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Forskningsöversikt (refereegranskat)abstract
- Background: The etiopathogenesis of psychiatric disorders is still not completely understood. Growing evidence supports the hypothesis that mental illness and related disturbances do not necessarily originate in the brain. Inflammation has been suggested to play a central role in psychiatric disorders and altered levels of peripheral cytokines have been reported in several studies. Recently, it has emerged that bacteria populating the human gut could modulate low-grade inflammation, as well as high-order brain functions, including mood and behavior. These bacteria constitute the microbiota, a large population comprising 40,000 bacterial species and 1,800 phila involved in key processes important to maintain body homeostasis. Method: In this review, we present and discuss studies exploring the role of dysbiosis and products of the gut-microbiota in the pathogenesis of psychiatric disorders, as well as their potential involvement in mediating the effect of antidepressants, mood stabilizers, and antipsychotics. Results: Although this field is still at its early stage of development, a growing number of studies suggest that an altered composition of the gut microbiota, together with translocation of bacterial products into the systemic circulation, might play a role in the pathogenesis of psychiatric disorders as well as in response to psychotropic medications. Conclusion: An altered composition and functioning of gut microbiota have been reported in psychiatric disorders, and recent findings suggest that gut bacteria could be involved in modulating the efficacy of psychotropic medications.
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| 12. |
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| 13. |
- Shoombuatong, Watshara, et al.
(författare)
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Towards Predicting the Cytochrome P450 Modulation : From QSAR to proteochemometric modeling.
- 2017
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 18:6, s. 540-555
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Tidskriftsartikel (refereegranskat)abstract
- Drug metabolism determines the fate of a drug when it enters the human body and is a critical factor in defining their absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics. Among the various drug metabolizing enzymes, cytochrome P450s (CYP450) constitute an important protein family that aside from functioning in xenobiotic metabolism is also responsible for a diverse array of other roles encompassing steroid and cholesterol biosynthesis, fatty acid metabolism, calcium homeostasis, neuroendocrine functions and growth regulation. Although CYP450 typically convert xenobiotics into safe metabolites, there are some situations whereby the metabolite is more toxic than its parent molecule. Computational modeling has been instrumental in CYP450 research by rationalizing the nature of the binding event (i.e. inhibit or induce CYP450s) or metabolic stability of query compounds of interest. A plethora of computational approaches encompassing ligand, structure and systems based approaches have been utilized to model CYP450-ligand interactions. This review provides a brief background on the CYP450 family (i.e. its roles, advantages and disadvantages as well as its modulators) and then discusses the various computational approaches that have been used to model CYP450-ligand interaction. Particular focus is given to the use of quantitative structure-activity relationship (QSAR) and more recent proteochemometric modeling studies. Finally, a perspective on the current state of the art and future trends of the field is provided.
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| 14. |
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| 15. |
- Hedlund, E, et al.
(författare)
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Cytochrome P450 in the brain; a review
- 2001
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002. ; 2:3, s. 245-263
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Tidskriftsartikel (refereegranskat)
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| 16. |
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| 17. |
- Tsoi, C, et al.
(författare)
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Sulfation in dog
- 2005
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002. ; 6:3, s. 275-285
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Ohayon, M. M., et al.
(författare)
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Prevalence, incidence, evolution and associated factors of sleep paralysis in a longitudinal study of the US general population
- 2022
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Ingår i: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 98, s. 62-67
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Sleep paralysis is a common phenomenon which causes and consequences are seldomly studied. The aim of this study was to investigate the incidence and prevalence of sleep paralysis (SP) in the American adult population and its evolution on a 3-year period.Methods: This longitudinal study was conducted between 2002 and 2015 and included a representative sample of the US general population. A total of 12,218 subjects were initially interviewed (W1) and 10,931 were re-interviewed three years later (W2). The subjects participated in telephone interviews using the Sleep-EVAL expert system. Each interview lasted for about 1 h. SP episodes were assessed according to their frequency and duration.Results: At W1, 9.7% (95%CI: 9.1%–10.3%) reported having ≥1 episode of SP in the previous year. At W2, 15.1% (95%CI: 14.4%–15.8%) reported SP. A total of 29.9% of subjects with SP at W1 still reported episodes at W2. The 1-year incidence was 2.7% (95%CI: 2.4–3.0%). After adjusting for age and sex, prevalent SP (i.e., present at W2) was predicted by age and race and the following factors present at W1: major depressive disorder, pain, hypersomnolence, cataplexy, hypnagogic and hypnopompic hallucinations, posttraumatic stress disorder, a reduction in sleep duration of ≥60 min, and the use of analgesic/antipyretic medication. Incident SP (i.e. new cases at W2) had similar predictive factors.Discussion: Episodes of SP are frequent in the general population. Its persistence is predicted by several factors associated with narcolepsy like hypersomnolence and cataplexy but also by other factors like posttraumatic stress disorder or pain.
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