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| 4. |
- Nijs, Jo, et al.
(författare)
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Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria
- 2023
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.
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| 5. |
- Polli, James E, et al.
(författare)
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Summary workshop report : bioequivalence, biopharmaceutics classification system, and beyond
- 2008
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 10:2, s. 373-379
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Tidskriftsartikel (refereegranskat)abstract
- The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.
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| 6. |
- Wyns, A., et al.
(författare)
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The Biology of Stress Intolerance in Patients with Chronic Pain-State of the Art and Future Directions
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the quality of life for individuals living with chronic pain. As stress has become a prevalent concern in modern society, understanding the connection between stress, HPA axis, ANS, and chronic health conditions such as chronic pain is crucial to improve public health and well-being.
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| 7. |
- Chu, X., et al.
(författare)
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Intracellular Drug Concentrations and Transporters : Measurement, Modeling, and Implications for the Liver
- 2013
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 94:1, s. 126-141
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Forskningsöversikt (refereegranskat)abstract
- Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism.This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.
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| 8. |
- Nijs, Jo, et al.
(författare)
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Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine
- 2021
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain
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| 9. |
- Selen, Arzu, et al.
(författare)
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The Biopharmaceutics Risk Assessment Roadmap for Optimizing Clinical Drug Product Performance
- 2014
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 103:11, s. 3377-3397
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Tidskriftsartikel (refereegranskat)abstract
- The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate learning and confirming studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile.
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| 10. |
- Bagardi, M, et al.
(författare)
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Influence of Morphometry on Echocardiographic Measurements in Cavalier King Charles Spaniels: An Inverse Probability Weighting Analysis
- 2021
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Ingår i: Veterinary sciences. - : MDPI AG. - 2306-7381. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- The development and progression of myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) are difficult to predict. Thus, the identification of dogs with a morphotype associated with more severe mitral disease at a young age is desirable. The aims of this study were to: (1) describe the physical, morphometric, and echocardiographic features of class B1 MMVD-affected Cavalier King Charles Spaniels (CKCS) according to the American College of Veterinary Internal Medicine (ACVIM) guidelines; (2) evaluate the influence of morphometric physical measurements on murmur intensity, mitral valve prolapse (MVP), regurgitant jet size, and indexed mitral valve and annulus measurements. Fifty-two MMVD-affected CKCS were included in the ACVIM class B1. This is a prospective clinical cross-sectional study. Morphometric measurements, which included the body, thorax, and head sizes of each dog, were investigated to establish the association with heart murmur intensity, valvular and annular echocardiographic measurements, MVP, and regurgitant jet size, using inverse probability weighting (IPW) analyses to adjust for confounding. The IPW analyses showed that when the head length and nose length decreased, dogs had a more severe regurgitant jet size. Furthermore, subjects with a more pronounced head stop angle had thicker anterior mitral valve leaflets. A brachycephalic morphotype, as seen in dogs similar to the King Charles Spaniel breed in terms of cephalic morphology, is associated with a more severe regurgitant jet size and with valvular characteristics that are related to the most severe forms of MMVD.
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| 11. |
- Benet, Leslie Z., et al.
(författare)
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The use of BDDCS in classifying the permeability of marketed drugs
- 2008
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Ingår i: Pharmaceutical research. - : Springer. - 0724-8741 .- 1573-904X. ; 25:3, s. 483-488
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Tidskriftsartikel (refereegranskat)abstract
- We recommend that regulatory agencies add the extent of drug metabolism (i.e., >or=90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence. That is, >or=90% metabolized is an additional methodology that may be substituted for >or=90% absorbed. We propose that the following criteria be used to define>or=90% metabolized for marketed drugs: Following a single oral dose to humans, administered at the highest dose strength, mass balance of the Phase 1 oxidative and Phase 2 conjugative drug metabolites in the urine and feces, measured either as unlabeled, radioactive labeled or nonradioactive labeled substances, account for >or=90% of the drug dosed. This is the strictest definition for a waiver based on metabolism. For an orally administered drug to be >or=90% metabolized by Phase 1 oxidative and Phase 2 conjugative processes, it is obvious that the drug must be absorbed. This proposal, which strictly conforms to the present>or=90% criteria, is a suggested modification to facilitate a number of marketed drugs being appropriately assigned to Class 1.
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| 12. |
- Fernandez-de-las-Penas, C., et al.
(författare)
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Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.
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| 13. |
- Hendrix, J., et al.
(författare)
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The interplay between oxidative stress, exercise, and pain in health and disease: Potential role of autonomic regulation and epigenetic mechanisms
- 2020
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 9:11, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain. This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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- Leemans, L., et al.
(författare)
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It Hurts to Move! Intervention Effects and Assessment Methods for Movement-Evoked Pain in Patients With Musculoskeletal Pain: A Systematic Review with Meta-analysis
- 2022
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Ingår i: Journal of Orthopaedic & Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 52:6, s. 345-374
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To estimate the effects of musculoskeletal rehabilitation interventions on movementevoked pain and to explore the assessment methods/protocols used to evaluate movement-evoked pain in adults with musculoskeletal pain. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: Three electronic databases (PubMed, Web of Science, and Scopus) were searched. STUDY SELECTION CRITERIA: Randomized controlled trials investigating musculoskeletal rehabilitation interventions for movement-evoked pain in adults with musculoskeletal pain were included. DATA SYNTHESIS: Meta-analysis was conducted for outcomes with homogeneous data from at least 2 trials. The mean change in movementevoked pain was the primary outcome measure. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: Thirty-eight trials were included, and 60 different interventions were assessed. There was moderate-certainty evidence of a beneficial effect of exercise therapy compared to no treatment (standardized mean difference [SMD], -0.65; 95% confidence interval [CI]: -0.83, -0.47; P<.001) on movement-evoked pain in adults with musculoskeletal pain. There was low-certainty evidence of a beneficial effect of transcutaneous electrical nerve stimulation compared to no treatment (SMD, -0.46; 95% CI: -0.71, -0.21; P=.0004). There was no benefit of transcutaneous electrical nerve stimulation when compared to sham transcutaneous electrical nerve stimulation (SMD, -0.28; 95% CI: -0.60, 0.05; P=.09; moderate-certainty evidence). CONCLUSION: There was moderate-certainty evidence that exercise therapy is effective for reducing movement-evoked pain in patients with musculoskeletal pain compared to no treatment. Consider exercise therapy as the first-choice treatment for movement-evoked pain in clinical practice.
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| 17. |
- Polli, A., et al.
(författare)
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Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia
- 2022
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM. Methods. A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-alpha, IFN-gamma, IL-6, and TGF-beta). Results. COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-beta expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-gamma expression in patients. Discussion Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.
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