Medicine Clinical Practice Research Articles

Chronic Stress-The Root Cause for All the Diseases

We all go through stress at some point of life but now a days,we have started to live in stress everyday because of the new age fast life coupled with wrong lifestyle habits. Stress affects all systems of the body including the musculoskeletal, respiratory, cardiovascular, endocrine, gastrointestinal, nervous and reproductive systems. Chronic stress will lead to cellular stress or cellular death, which will straight away make you embrace chronic diseases. It has not been easy to integrate this evidence linking psychiatric illness and mental stress with the development of cardiovascular disease into the clinical practice of medicine.

A Survey on Korean Medicine Doctors’ Recognition for Developing Korean Medicine Clinical Practice Guidelines for Gastric Cancer

Objective: The purpose of this study was to provide data for the development of Korean medicine (KM) clinical practice guidelines (CPG) for gastric cancer (GC) by identifying the awareness and knowledge needs of KM doctors (KMD) through an online survey.Methods: A survey questionnaire was produced by referring to the previous recognition survey studies for clinical KMDs. The survey questionnaire was composed of questions regarding the current status of clinical care for GC, the knowledge level of clinicians about GC, and other details that clinicians use during practice. The survey was conducted from September 20 to October 22, 2021. An online survey was conducted with 195 KMDs from the Society of Korean Medicine and the Korean Association of Traditional Oncology of KM.Results: A total of 195 respondents participated in the online survey regarding the current status of GC treatment. Of this number, 10.3% of the respondents specialize in GC, but even if they do not currently specialize in GC, they are more likely to treat patients with GC in the future. In terms of the specifics of KM treatment, there was a demand for information on comprehensive KM treatment methods, such as herbal medicine, acupuncture, moxibustion, cupping, and chuna, as well as on analyzing the effectiveness of combined treatment with chemotherapy and radiation.Conclusion: In this study, we were able to understand the clinical KMDs’ perception of GC, knowledge level, and requirements in the CPG. The results of this study will provide the basic data for the development of CPG for GC.

National Health Insurance Data Analysis for the Second-Wave Development of Korean Medicine Clinical Practice Guidelines in South Korea

National Health Insurance Data Analysis for the Second-Wave Development of Korean Medicine Clinical Practice Guidelines in South Korea

0573 Application of AASM Clinical Significance Thresholds to Once-Nightly Sodium Oxybate for Improvement in Narcolepsy Symptoms

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release treatment, was evaluated for the treatment of narcolepsy in adults in the phase 3 REST-ON clinical trial (NCT02720744). The 3 co-primary endpoints, mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement rating, and weekly number of cataplexy attacks (NCA), and the secondary endpoint of Epworth Sleepiness Scale (ESS) score were significant for ON-SXB vs placebo at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose; all P< 0.001). These data were published after the cutoff for inclusion in the American Academy of Sleep Medicine (AASM) clinical practice guidelines for narcolepsy treatment; thus, REST-ON results were analyzed according to AASM clinical significance thresholds (CSTs). Methods Individuals with narcolepsy type 1/2 and age ≥16 years were randomized 1:1 to receive double-blind ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or matching placebo. For each dose (6 g, week 3; 7.5 g, week 8; and 9 g, week 13), least-squares mean (LSM) difference from placebo was calculated for change from baseline in mean sleep latency on the MWT, ESS score, and percentage reduction in NCA. As defined in the 2021 AASM guidelines, CSTs were the following changes vs placebo: MWT, ≥2-minute increase; ESS, ≥2-point decrease; and cataplexy, ≥25% decrease in NCA. Results 190 participants (ON-SXB, n=97; placebo, n=93) were in the modified intent-to-treat population. On the MWT, difference in LSM change from baseline was 5.0, 6.2, and 6.1 minutes for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM change from baseline ESS scores were −2.1, −3.2, and −3.9 for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM percentage reduction in NCA were 26.0%, 34.2%, and 36.1% for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Conclusion Clinically significant improvement in excessive daytime sleepiness and cataplexy per AASM-established criteria was met with ON-SXB 6, 7.5, and 9 g doses. If FDA approved, ON-SXB will provide a once-nightly treatment for improving EDS and cataplexy in adults with narcolepsy. Support (if any) Avadel Pharmaceuticals

0260 Establishment of a polysomnography databank for sleep disorders in Japan

Abstract Introduction Polysomnography (PSG) has been suggested to be useful as an objective indicator (biomarker) that contributes to the diagnosis and severity evaluation of various sleep disorders. However, its regular use is still limited to the specialized institutions for sleep disorders. Therefore, PSG is essential for clinical diagnosis of only some sleep disorders, and further application of PSG in conjunction with biomarker development of disorders including such as insomnia, and psychiatric disorders with comorbid sleep disorders is expected. The aim of this project is to establish a PSG databank for sleep disorders in collaboration with major PSG laboratories in Japan. Methods This project is collaborated with medical and research institutions that conduct PSG on a large scale in Japan. The National Center of Neurology and Psychiatry (NCNP) serves as the core institution. The initial collaborating institution is the Tokyo Medical University, which is in cooperation with the Yoyogi Sleep Disorder Center, the largest PSG facility in the Kanto region. We also collaborate with three other core PSG facilities in the Kanto, Tohoku and Kyushu regions: the Nihon University, the Akita University (in cooperation with the Akita Sleep Clinic), and the Kurume University. This project has been approved by the Ethics Committee of the NCNP. Results We have stored about 3,000 PSG data evaluated by the standard of the American Academy of Sleep Medicine clinical practice guideline or the traditional Rechtschaffen & Kales standard with adjunct clinical metadata for the past 9 years at the NCNP, about 17,900 at the Tokyo Medical University, about 1,900 at the Nihon University, about 500 at the Akita University, and about 3,000 at the Kurume University. We are continuously collecting and banking data for enhancing research availability of the PSG databank for sleep disorders. Conclusion The collected data will be used for research on the development of objective indices for sleep disorders or neuropsychiatric disorders, for which objective indices are lacking in diagnosis and pathological evaluation. Support (if any) This work was supported by the Intramural Research Grant (#2-1) for Neurological and Psychiatric Disorders of NCNP.

Integrated serum pharmacochemistry, network pharmacology and pharmacokinetics to explore bioactive components of Gushudan in the treatment of osteoporosis

Gushudan (GSD), a compound prescription on the basis of traditional Chinese medicine (TCM) theory and clinical practice, has been used in the treatment of osteoporosis (OP) for many years. Although studies have shown that GSD can treat OP, there is a lack of systematic screening method to explore the bioactive components, which are still unclear. Therefore, this study was aimed to establish an integrated method to screen and determine bioactive ingredients of GSD in the treatment of OP by serum pharmacochemistry, network pharmacology and pharmacokinetics. Firstly, 112 components of the GSD extract and 90 serum migrating constituents were identified by the ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), most of which were derived from flavonoids, tanshinones, coumarins and organic acids. Secondly, based on the network pharmacological analysis of the serum migrating constituents, 37 core targets and 20 main pathways related to both GSD and OP were obtained. More importantly, 7 bioactive ingredients were further screened as the PK markers by the network topology parameters including icariin, icariside II, isopimpinellin, bergapten, imperatorin, osthole and tanshinone IIA. Finally, a sensitive and accurate quantitative method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated for simultaneous determination of the 7 bioactive ingredients in the rat plasma after oral administration of GSD extract, which was then applied to pharmacokinetic study. Besides, the overall pharmacokinetic characteristics were further calculated: Cmax was 180.52 ± 31.18 ng/mL, Tmax was 0.46 ± 0.20 h, t1/2 was 4.09 ± 0.39 h, AUC0-∞ was 567.24 ± 65.29 ng·h/mL, which displayed quick absorption and medium elimination in rats after oral administration of GSD extract. This study provided a new and holistic insight for exploring bioactive constituents and main targets to decode the therapeutic material basis of GSD against OP.

Challenges of evidence based medicine in clinical practice

Evidence-based medicine (EBM) is an approach by clinicians that involves conscientious, explicit, and judicious use of available evidence in deciding on the care of individual patients.1 With the digital revolution and easy access to the available literature, EBM , which was not very practical a few decades ago due to the difficulty in assessing the resources, has been practiced with increasing success nowadays, even in the developing world. The revolution brought about by EBM with regard to the practice of medicine over the past few decades has been remarkable.2 Because of the individualized treatment based on external evidence, EBM leans towards justifying the action with accountability; hence being labeled as the fourth revolution in American Medicine.3

Chapitre 5. L’impact de la pandémie de COVID-19 sur l’évolution du paradigme éthique de la médecine clinique en Russie (« à la guerre comme à la guerre »)

The CОVID-19 pandemic became a catalyst for the transformation of the ideas of the existence of global ethics in favor of real moral pluralism, exposed the problem of abandoning the principles of personalized medicine in favor of public health ethics (collective ethics of civil society). The authors sequentially analyze the objective factors that influenced the change in the moral paradigm of the clinical medicine in Russia: the peculiarities of the course of infection, the lack of resources in the health-care sector, the inability to use advanced treatment methods in different groups of patients, the protection of medical workers, the provision of emergency and planned surgical interventions, and the prevention of further spread of infection. In addition, the moral consequences of the use of administrative measures to limit the spread of the pandemic are given: restriction of social contacts, the use of personal protective equipment, retraining of specialists, re-profiling of the bed fund, leveling problems of communication with colleagues, patients and students. Special attention is paid to the problem of “anti-vaxxers”, representing a significant part of society and hindering the implementation of the vaccination program of the population. We believe that active and passive protest against vaccinations lie not in a rational plane, but in an emotional one, in an immanent distrust of the state and its institutions. Thus arises a secondary ethical problem of the state’s responsibility for the life and health of every citizen, regardless of their beliefs. Contradictions in the moral principles of individual strata of the population (including groups like those who agree to get vaccinated, those who doubt, the indifferent ones, “active anti-vaccinators”) currently seem irreconcilable due to the state’s detachment from solving moral problems.Ethic divergence in the context of the pandemic has become real, stable and difficult to overcome, while the claims of a single, global, global bioethics are being questioned. The COVID-19 pandemic has formulated the ethical task of the 21st century, which will have to be the development of public policy and practice of clinical medicine in the context of serious moral contradictions and significant bioethical differences.

Ultrasound Elastography in the Evaluations of Tendon-Related Disorders—A Systematic Review

Tendon-related disorders are a common condition in both sports medicine and orthopedic clinical practice. Ultrasonography, power doppler, and magnetic resonance imaging (MRI) are the most widespread technologies, but the use of ultrasound elastography—including strain elastography and shear wave elastography—has been increasing in the last years. The aim of this paper is to evaluate the use of ultrasound elastography in tendon-related disorders. Research in PubMed, Scopus, and Web of Science databases is performed, and 364 papers are exported. After the study selection process, 38 papers are included in this systematic review. The risk of bias of each paper is evaluated using the RoBANS tool. Blinding, confounding variables, and measurement of exposure are the most affected items. From the included papers, tendinopathy is the most analyzed pathology, followed by tenosynovitis and rotator cuff disease. The Achilles tendon, patellar tendon, and common extensor tendon of the hand are the most analyzed tendons. Ultrasound elastography results in being the method providing good sensitivity and specificity (up to 100% and 100%, respectively, in tendinosis of the long head of the biceps tendon, in transverse plan examination) and accuracy (up to 97.8% in Achilles tendinopathy); furthermore, this technique is able to ensure real-time feedback on tissue elasticity and appears more sensitive than B-mode alone.

Sequencing and combination of current small-molecule inhibitors for chronic lymphocytic leukemia: Where is the evidence?

Small-molecule inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL), a landscape once dominated by chemoimmunotherapy (i.e., an anti-CD20 monoclonal antibody in combination with systemic chemotherapy) in fit and unfit individuals. Key challenges include the management of refractory disease as well as the optimization of the therapy sequence. Decreased responsiveness has been observed with prolonged treatment, especially with Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) inhibitors which are given continuously, while venetoclax, an agent that targets dysregulations in intrinsic apoptosis signaling, has a fixed duration when combined with anti-CD20 monoclonal antibodies or BTK inhibitors. Combination therapy aims to synergistically target different oncogenic signaling pathways to abrogate the proliferation of resistant clones and thereby allows for fixed-duration treatments. An advantage of fixed-duration therapy is the potential to decrease financial and drug-induced toxicities. Sequencing of therapies is important to individualize treatment decisions based on factors such as age, comorbidities, tolerability, and patient preferences. However, to date, there are limited data to guide the rational sequencing or combination of these therapies, since conventional chemoimmunotherapy or chemotherapy regimens were used as comparators against these small-molecule inhibitors in trials that led to their regulatory approvals. In this article, we examined and evaluated the current evidence for sequencing versus the combination of small-molecule inhibitors for CLL by conducting comprehensive searches of the United States National Library of Medicine PubMed database, key meeting abstracts, and clinical practice guidelines. We also summarized findings from expert opinions to elucidate best practices for clinical scenarios with limited evidence to guide treatment selection.

Renal herb formula protects against hyperuricemic nephropathy by inhibiting apoptosis and inflammation

BackgroundHyperuricemic nephropathy may be induced by the elevation and accumulation of uric acid in kidney after hyperuricemia, which leads to kidney residential cells apoptosis and inflammation. Renal herb formula (RHF) is a self-designed formula based on traditional Chinese medicine theory and clinical practice in kidney disease treatment. In the literature available currently, there is not yet research article reporting the reno-protective effect of RHF against hyperuricemic nephropathy. PurposeThis study was performed to analyze the bioactive compound profiles of RHF, evaluate its protective effects against hyperuricemic nephropathy, and investigate the mechanisms of actions regarding apoptosis and inflammation. MethodsUltra-performance liquid chromatography with a diode-array detector was applied to establish fingerprint and chemical composition of RHF. Potassium oxonate was used to induce hyperuricemic nephropathy in mice, and uric acid was used to stimulate apoptosis and inflammatory response in HK-2 cells, while the mice and cells were treated with RHF to explore its reno-protective effects and mechanisms. ResultsIt was found that chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A-C may be the characteristic components of RHF. RHF treatment could improve kidney functions in mice with hyperuricemic nephropathies, such as decreasing urine protein, uric acid, and creatinine and serum uric acid, creatinine, and urea nitrogen. Histopathological observations showed that RHF treatment ameliorated kidney glomerular hypotrophy, tubular damage, and inflammatory infiltration. Mechanism studies revealed that RHF inhibited kidney residential cell apoptosis and inflammatory response by targeting the p53-associated intrinsic apoptosis pathway and NF-κB-mediated inflammatory pathway. ConclusionTaken together, it could be concluded that RHF exerted reno-protective effects against hyperuricemic nephropathy through reducing apoptosis and inflammation. RHF and the bioactive compounds chlorogenic acid analogs as promising candidates may be developed into novel and effective drugs for hyperuricemic nephropathy treatment and management.

Dichotomine B Attenuates Neuroinflammatory Responses by Regulating TLR4/MyD88-mTOR Signaling Pathway in BV2 Cells.

Dichotomine B is a [Formula: see text]-Carboline alkaloid isolated from Stellariae Radix. Stellariae Radix, also known as Yin Chai Hu, is a common Chinese medicine in clinical practice. This herb has been demonstrated to have anti-inflammatory activity. This study aimed to investigate the effects and mechanisms of Dichotomine B on neuroinflammation by BV2 microglia induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The experiment was divided into a control group, a model group (10 µg/mL LPS + 5 mM ATP), a model+ TLR4 inhibitor (TAK-242, 10 µmol/L) group, model+ Dichotomine B (20, 40 and 80 µmol/L) groups and Dichotomine B (80 µmol/L) group. The BV2 cell viability was detected by MTT assay, the morphology of BV2 cells was observed by inverted microscope, and the levels of IL-6, IL-1[Formula: see text] and TNF-[Formula: see text] in BV2 cells were determined by ELISA. The expression levels of TLR4, MyD88, p-mTOR/mTOR, p62, p-RPS6/RPS6, LC3II/LC3I and Beclin-1 proteins were detected by western blot assay. The expression levels of TLR4, MyD88, mTOR, p62, RPS6, LC3B and Beclin-1 mRNA were detected by PCR assay. Finally, molecular docking was performed to predict the affinity of Dichotomine B with TLR4, MyD88 and mTOR by LibDock of Discovery Studio and MOE. The results showed that compared with the model group, the survival rates of damaged cells were significantly increased by TAK-242 and Dichotomine B, and the morphology of these BV2 cells improved. The levels of IL-6, IL-1[Formula: see text] and TNF-[Formula: see text] were significantly decreased by TAK-242 and Dichotomine B in LPS/ATP-induced BV2 cells. 80 µmol/L Dichotomine B has no effect on normal BV2 cells. Further mechanism investigation showed that TAK-242 and Dichotomine B significantly inhibited the protein and mRNA expression levels of TLR4, MyD88, p-mTOR/mTOR (mTOR), p62, p-RPS6/RPS6 (RPS6) and increased the protein and mRNA expression levels of LC3II/LC3I (LC3B), Beclin-1. Docking study showed the LibDock scores of Dichotomine B with TLR4, MyD88 and mTOR were all higher than those of positive drugs (Diazepam). These findings indicated that Dichotomine B attenuated neuroinflammatory responses in LPS/ATP-induced BV2 microglia, and its mechanism may be related to TLR4/MyD88-mTOR signaling pathway and autophagy.

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system. It is a complex and heterogeneous disease, and its pathogenesis is still not completely understood. Precision medicine, which involves the use of advanced technologies such as genomics, proteomics, metabolomics, and imaging to identify specific biomarkers and disease subtypes, is a promising approach to the management of multiple sclerosis. Precision medicine in MS includes the development of targeted therapies that aim to modulate specific immune pathways involved in MS pathogenesis. This review article aims to provide an overview of the current status and future directions of precision medicine in MS. The article discusses the importance of precision diagnostics in MS, including the identification of biomarkers and imaging techniques for MS, as well as the challenges and opportunities of personalized treatment in MS. Targeted therapies in MS are also discussed, including the challenges of developing and implementing these therapies. The article highlights the potential of combination therapies in MS, and the role of AI and ML in improving biomarker identification. The challenges of implementing precision medicine in clinical practice are also addressed, including the standardization of diagnostic criteria and treatment guidelines, and the ethical and legal considerations of personalized treatment. Overall, precision medicine represents a promising approach to the management of MS, with the potential to improve diagnosis, prognosis, and treatment outcomes. However, the implementation of precision medicine in MS clinical practice requires addressing several challenges, including the standardization of diagnostic criteria and treatment guidelines, and the development of affordable and accessible technologies and therapies. With continued research and advances in technology, precision medicine has the potential to transform the field of MS research and clinical practice.

Can a Holistic View Facilitate the Development of Intelligent Traditional Chinese Medicine? A Survey

Intelligent traditional Chinese medicine (ITCM) is an emerging interdisciplinary subject. It aims to efficiently and precisely promote the prevention and treatment of diseases and health management in Chinese medicine clinical practice via the combination of traditional Chinese medicine (TCM) fundamentals and artificial intelligence technologies. Presently, it is experiencing dramatic growth in recent years. On the one hand, a holistic view, as a crucial philosophy in the theory of TCM, will be guiding the development of ITCM. On the other hand, a comprehensive discussion of the benefits of such a holistic view of ITCM is lacking. To this end, we conduct this survey by introducing the named holistic view first. Then, adaptive learning and field theory will be presented and discussed with respect to their application in ITCM. Ethical issues of ITCM will then be taken into account by human-centered TCM and potentials based on affective computing of ITCM. In addition, we give our opinions and insights on the challenges and open issues regarding the future of ITCM. We hope that this survey article can be a good guide for experts in the relevant fields.

Regulatory Approval, Reimbursement, and Clinical Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic Breast Cancer in the Netherlands

This study found that CDK4/6 inhibitors rapidly reached many eligible patients with metastatic breast cancer and were adopted gradually over time in the Netherlands. Adoption of innovative medicines may be further optimized, and better transparency of the availability of new medicines during different phases of the postapproval access pathway is needed. This cohort study reviewed approval and reimbursement decisions of the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib and estimated the number of patients with metastatic breast cancer who were eligible for these medicines compared with the actual use in clinical practice. The study used nationwide claims data that were obtained from the Dutch Hospital Data. Claims and early access data for patients with hormone receptor-positive and ERBB2 (formerly HER2)-negative metastatic breast cancer who were treated with CDK4/6 inhibitors from November 1, 2016, to December 31, 2021, were included. The number of new cancer medicines that are being approved by regulatory agents is increasing exponentially. Yet little is known about the pace at which these medicines reach eligible patients in daily clinical practice during different phases of the postapproval access pathway. Description of the postapproval access pathway, monthly number of patients who were treated with CDK4/6 inhibitors in clinical practice, and estimated number of patients who were eligible for treatment. Aggregated claims data were used, and patient characteristics and outcomes data were not collected. To describe the entire postapproval access pathway of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the Netherlands, from regulatory approval to reimbursement and to investigate the adoption of these medicines in clinical practice among patients with metastatic breast cancer. Three CDK4/6 inhibitors have received European Union-wide regulatory approval for the treatment of HR-positive and ERBB2-negative metastatic breast cancer since November 2016. In the Netherlands, the number of patients who have been treated with these medicines increased to approximately 1847 (based on 1 624 665 claims over the entire study period) from approval to the end of 2021. Reimbursement for these medicines was granted between 9 and 11 months after approval. While awaiting reimbursement decisions, 492 patients received palbociclib, the first approved medicine of this class, via an expanded access program. By the end of the study period, 1616 patients (87%) were treated with palbociclib, whereas 157 patients (7%) received ribociclib, and 74 patients (4%) received abemaciclib. The CKD4/6 inhibitor was combined with an aromatase inhibitor in 708 patients (38%) and with fulvestrant in 1139 patients (62%). The pattern of use over time appeared to be somewhat lower compared with the estimated number of eligible patients (1847 vs 1915 in December 2021), especially in the first 2.5 years after approval.

Community pharmacists' knowledge of substandard and falsified medicines in clinical practice: a cross-sectional survey in Saudi Arabia.

The main objective of this study was to explore community pharmacists' knowledge of substandard and falsified medicines (SFs). A descriptive cross-sectional study was conducted with community pharmacists in the Kingdom of Saudi Arabia using a pre-validated electronic survey. Ninety-two community pharmacists participated in this study. Many of the respondents (68.5%) had no experience with identifying SFs. We identified a concerning trend of under-reporting SFs (P < 0.003). Respondents reported that SFs constitutes 1-5% of medicines, with weight loss medicines being the most targeted for falsification. Most of the respondents had a low level of awareness about the newly implemented anti-counterfeit system in Saudi Arabia called the 'Drug Track and Trace System' (28.3% not really, 23.1% not at all). Respondents showed low levels of knowledge about technologies available to detect SFs (P < 0.01). Community pharmacists' self-reported awareness and knowledge of SFs in Saudi Arabia was inadequate; this deficiency may affect their ability to protect their patients from potential harm by combating SFs. As a regulatory body responsible for issues related to SFs, the Saudi Food and Drug Authority should develop an action plan to equip community pharmacists with training in SFs to enhance their ability to respond to SFs.

Predictive, preventive, personalized and participatory medicine (4P): narrative review

4 P medicine is a concept used in healthcare and biomedical research that is based on the principles of prediction, personalization, prevention, and participation. It is increasingly used which has enabled the rapid development of medicine: several forms/types of pathologies have been discovered, for which specific treatments and appropriate prevention strategies have been developed, it has become possible to predict the evolution of health and disease, all these would be useless without the participation of the patient, family, and decision makers.The purpose of this article is to provide an overview of the 4 P medicine and its preventive, predictive, personalized, and participatory principles through the lens of clinical practice.Materials and Methods: The database was searched for the keywords “4P medicine”, “personalized medicine”, “participatory medicine”, “systems medicine”. For the term “systems medicine” we obtained 5,257,904 results, in the last 10 years - there were 2,396,921 publications, journal articles - 2.4 million citations, book chapters - 11 thousand, related to medicine - 1.6 million of the references. For the term “precision medicine” 158,239 references appeared, for “personalized medicine” - 91,883 citations and for “participatory medicine” - 17,579 references. Most references were published in English. For the search for “personalized medicine oncology” - 18,209 references appeared, for “personalized medicine neurology” 4,751 references were discovered, in the last 10 years 4,336 of them were published, being journal articles4,300 and 16 book chapters. Most publications talk about the use of the principles of personalized medicine (4P) in demyelinating pathologies, epilepsy, dementia, neuro-oncology, stroke, migraine, neuroimaging, and neurorehabilitation. Results and discussions: 4P medicine is at the intersection of three major trends: the growing ability of systems biology and medicine to decipher the biological complexity of pathologies, the digital revolution that has increased theability to collect, integrate, store, analyze and communicate data and information, and consumer access to information.Conclusion: 4P medicine is a concept used in biomedical research and human health care that was taken from systems biology and systems medicine. It is a form of approach that uses the principles of prevention, prediction, personalization, and participation to transform healthcare from a reactive to a proactive one. The use of the principles of 4P medicine in clinical practice allows the deciphering of forms of the disease, the stratification according to pathophysiological mechanisms, the application of personalized treatment to the patient, respectively more efficiently and with fewer adverse reactions.

XIII National Congress of the Research Group in Psychosomatics (RGP).

This Supplement of La Clinica Terapeutica includes abstracts of lectures, symposia, workshops, clinical case presentations and posters of the XIII National Congress of the Research Group in Psychosomatics (GRP). The themtic of Congress is "Multidisciplinarity in psychosomatic perspective" and it represents and ambitious event realized by debating of clinicians of healthcare system. Psychosomatics represents an extraordinary opportunity to improve clinical practice in medicine, psychiatry and clinical psychology by integrating biological, psychological and social factors. The bio-psycho-social model is still the theoretical and practical core of psychosomatics. It allows clinicians to see disease as the result of mechanisms of interaction at the cellular, interpersonal and environmental levels that include personality and familiarity. The congress organized by the GRP for 2023 highlights multidisciplinary approach as a science at the service of psychosomatics capable of providing the clinical tools that allow a complete and accurate assessment according to the principles of the bio-psycho-social model. It allows clinicians to see disease as the result of mechanisms of interaction at the cellular, interpersonal and environmental levels that include personality and familiarity. Such indices are expected to be, among the others, sensitive in recording changes over time, capable of providing additional information according to the principle of incremental validity, able to investigate the person in the complexity linked to suffering and resources. This approach can be an antidote to the reductionist models that clash with clinical reality and that make the patient's visit a kind of distracted listening and subsequent random prescription. Multidisciplinarity and psychosomatic assessment thus become essential in clinical practice and research. The abstracts document how psychosomatics in clinical practice is more timing than ever and adequate for give a home to researchers and clinicians who want to venture off the beaten and clinically unsatisfactory paths of standard nosography.

Disulfiram—Mitigating Unintended Effects

Lyme disease caused by infection with a multitude of vector-borne organisms can sometimes be successfully treated in its very early stages. However, if diagnosis is delayed, this infection can become disseminated and, like another spirochetal infection syphilis, can affect multiple organ systems in the body, causing a wide variety of life-altering symptoms. Conventional antibiotic therapy may not be effective in eradicating the symptoms of the disease we know as Lyme disease. The recent literature has suggested that disulfiram (DSM) may be a potent drug in the armamentarium of physicians who treat chronic Lyme disease. The use of disulfiram in the treatment of Lyme disease started with a researcher who determined that DSM is bactericidal to spirochete. Encouraged by published case reports of apparent recovery from chronic Lyme disease, having prescribed DSM ourselves in the past for alcoholics who had a desire to stop drinking and prescribing it now for patients with chronic Lyme disease, we observed both predictable and potentially avoidable side effects not necessarily related to the ingestion of alcohol. We reviewed the published literature in PubMed and Google Scholar, using the following key words: Lyme Disease; Borrelia burgdorferi treatment; and disulfiram toxicity. This paper outlines the results of that research to help avoid some of the pitfalls inherent in this novel use of an old and established medication in the practice of clinical medicine.

Effects of Atractylodes Macrocephala Rhizoma polysaccharide on intestinal microbiota composition in rats with mammary gland hyperplasia.

In recent years, mammary gland hyperplasia (MGH) has been considered to be one of the diseases caused by endocrine disorders. It has been shown that diseases caused by endocrine disorders can be treated by regulating intestinal microbial. As a commonly used medicine in clinical practice, Atractylodes Macrocephala Rhizoma has good functions in regulating intestinal homeostasis. Therefore, this paper studied the effect of Atractylodes Macrocephala Rhizoma polysaccharide (AMP) on the intestinal flora of MGH rats, providing a new idea for polysaccharide treatment of MGH. Eighteen female SD rats were selected and randomly divided into three groups: blank control group (Con), model control group (Mod), and AMP group, six rats in each group. MGH rat models were established by estradiol-progesterone combination and treated with AMP gastric infusion. The levels of E2, P, and PRL in the serum of rats were measured, the intestinal contents were collected, and 16s rRNA high- throughput sequencing technology was analyzed the changes of intestinal flora in the MGH rats. AMP has good therapeutic effects on MGH rats, decreasing estradiol (E2) and prolactin (PRL) levels and increasing progesterone (P) levels; at the same time, it can regulate the abundance and diversity of intestinal flora of MGH rats, improve the disorder of intestinal flora caused by MGH, and change the community structure, increase the abundance of beneficial flora, and decrease the abundance of pathogenic flora. AMP can improve the intestinal microbiological environment of MGH rats, maintain the microecological balance of intestinal microbial, and improve MGH symptoms.