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      Differential clinical characteristics across traditional Chinese medicine (TCM) Syndromes in patients with sickle cell disease

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          Abstract

          Background

          Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effects for pain management in SCD. However, these clinical studies lack the guidance of Traditional Chinese Medicine (TCM) Syndrome Differentiation principles for treatment.

          Aim

          To characterize differences in clinical presentation amongst TCM diagnosed Syndromes in SCD patients.

          Method

          Fifty-two patients with SCD and 28 age- and sex-matched healthy controls (HCs) were enrolled in an ongoing trial of acupuncture. Each participant completed a series of questionnaires on pain, physical function, fatigue, sleep, anxiety, depression and QoL and underwent cold- and pressure-based quantitative sensory testing at baseline. Data on prescription opioid use over the 12 months prior to study enrollment was used to calculate mean daily morphine milligram equivalents (MME). Differences among the three TCM Syndromes were analyzed by one-way ANOVA followed by Tukey post hoc testing. Two-sample t-tests were used to compare SCD and HC groups.

          Results

          TCM diagnosis criteria classified SCD patients into one of three TCM Syndromes: (a) Equal; (b) Deficiency; and (c) Stagnation. The Stagnation group exhibited higher pain interference, physical dysfunction, nociplastic pain, fatigue, anxiety, depression, MME consumption and lower sleep quality and QoL compared to the Equal group. Few differences were observed between HCs and the Equal SCD group across outcomes. Deficiency and Stagnation groups were differentiated with observed- and patient-reported clinical manifestations.

          Conclusion

          These findings suggest that TCM diagnosed Syndromes in SCD can be differentially characterized using validated objective and patient-reported outcomes. Because characteristics of pain and co-morbidities in each SCD patient are unique, targeting specific TCM “Syndromes” may facilitate treatment effectiveness with a Syndrome-based personalized treatment plan that conforms to TCM principles. These findings lay the foundation for the development of tailored acupuncture interventions based on TCM Syndromes for managing pain in SCD. Larger samples are required to further refine and validate TCM diagnostic criteria for SCD.

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          Most cited references54

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          painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.

          Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities. In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD-Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients. The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co-morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component. Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.
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            Fibromyalgia: a clinical review.

            Fibromyalgia is present in as much as 2% to 8% of the population, is characterized by widespread pain, and is often accompanied by fatigue, memory problems, and sleep disturbances.
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              Mortality in sickle cell disease. Life expectancy and risk factors for early death.

              Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-beta-thalassemias) is needed to counsel patients, target therapy, and design clinical trials. We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death. Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy.
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                Author and article information

                Contributors
                Journal
                Front Pain Res (Lausanne)
                Front Pain Res (Lausanne)
                Front. Pain Res.
                Frontiers in Pain Research
                Frontiers Media S.A.
                2673-561X
                2673-561X
                05 January 2024
                2023
                : 4
                : 1233293
                Affiliations
                [ 1 ]Department of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine , Indianapolis, IN, United States
                [ 2 ]Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine , Indianapolis, IN, United States
                [ 3 ]Center for Integrative Health, The Ohio State University , Columbus, OH, United States
                [ 4 ]Indiana University Simon Cancer Center , Indianapolis, IN, United States
                [ 5 ]Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School , Ann Arbor, MI, United States
                [ 6 ]Department of Anesthesiology and Perioperative Care, School of Medicine, Susan Samueli Integrative Health Institute, University of California , Irvine, Irvine, CA, United States
                Author notes

                Edited by: Keesha Roach, University of Tennessee Health Science Center (UTHSC), United States

                Reviewed by: Girindra Raval, Augusta University, United States

                Cristian Acosta, Conicet Mendoza, Argentina

                [* ] Correspondence: Ying Wang ywa12@ 123456iu.edu
                Article
                10.3389/fpain.2023.1233293
                10796810
                38249565
                9ffd28cc-3c2b-4bf1-b440-1e10cf1c1c66
                © 2024 Wang, Wang, Pucka, O'Brien, Harte and Harris.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 June 2023
                : 11 December 2023
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 55, Pages: 0, Words: 0
                Funding
                Funded by: NIH K99/R00
                Award ID: 5R00AT010012
                Funded by: Indiana University Health—Indiana University School of Medicine Strategic Research Initiative
                Award ID:  
                This work was supported by NIH K99/R00 award (Grant # 5R00AT010012) and Indiana University Health—Indiana University School of Medicine Strategic Research Initiative funding to YW.
                Categories
                Pain Research
                Original Research
                Custom metadata
                Pharmacological Treatment of Pain

                sickle cell disease,pain,traditional chinese medicine,syndrome differentiation,acupuncture,patient-reported outcomes,quantitative sensory testing,morphine milligram equivalents

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