Probiotics use for antibiotic-associated diarrhea: a pragmatic participatory evaluation in nursing homes.

BACKGROUND: Antibiotic-associated diarrhea (AAD) occurs in 2-25% of nursing home residents, which may lead to dehydration, malnutrition, severe complications and hospitalizations. Research shows that probiotics can be effective and safe in reducing AAD. However, probiotics are not routinely used in Dutch nursing homes. The objectives of this evaluation were to develop a procedure for the implementation of probiotics to prevent AAD in nursing homes, to evaluate effects on AAD occurrence, and to evaluate the implementation process of probiotics in daily care. METHODS: A pragmatic participatory evaluation (PPE) design was chosen, as it seemed a suitable approach for implementation of probiotics, as well as for evaluation of its effectiveness in daily nursing home practice. Probiotics administration was implemented in three nursing homes of the Rivas Zorggroep for residents with somatic and/or psychogeriatric conditions. Ninety-three residents provided data on 167 episodes of antibiotics use, of which 84 episodes that included supplementation with probiotics and 83 episodes with no probiotics supplementation. A multispecies probiotics was administered twice daily upon start of antibiotic treatment, up to 1 week after completing the antibiotics course. The occurrence of AAD was monitored and a process evaluation was conducted to assess facilitators and barriers of probiotics implementation. RESULTS: The number of episodes with AAD when using probiotics was significantly lower than when no probiotics was used (20% vs 36%; p = 0,022, Chi-square). No significant differences in the occurrence of AAD were found between the residents taking amoxicillin/clavulanic acid or ciprofloxacin. Reported facilitators for implementation were perceived benefits of probiotics and prescription by medical staff. Reported challenges were probiotics intake by residents and individual decision-making as to which resident would benefit from it. CONCLUSION: Successful implementation of probiotics demonstrated the prevention of AAD in nursing home residents. TRIAL REGISTRATION: ISRCTN 94786163, retrospectively registered on 3 February 2020.

Development of an evidence-based decision aid on complementary and alternative medicine (CAM) and pain for parents of children with cancer.

PURPOSE: To develop an evidence-based decision aid for parents of children with cancer and to help guide them in the use of complementary and alternative medicine (CAM) for cancer care. METHODS: This study had a mixed research design. The needs of parents were investigated by survey and focus group. A systematic review and meta-analysis were performed on the effectiveness of CAM using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Clinical experts were interviewed and a decision aid on CAM treatment for pain was developed. RESULTS: Parents emphasized the importance of reliable information on CAM, focusing primarily on communication and a broad spectrum of complaints related to cancer treatment. The decision aid on CAM for pain included five modalities based on 11 randomized control trials (RCTs): hypnotherapy, mind-body techniques, massage, healing touch, and music therapy. Meta-analysis could be performed on hypnotherapy, which significantly reduced cancer-related procedural pain compared with standard care (MD, - 1.37; 95% CI, - 1.60, - 1.15; P < 0.00001) and attention control (MD, - 1.13; 95% CI, - 1.34, - 0.94; P < 0.00001), and massage, demonstrating no effect on pain compared with standard care (MD, - 0.77; 95% CI, - 1.82, 0.28; P = 0.15). Research evidence and supplementary information from clinical practice and patient were incorporated in a website-based decision aid. CONCLUSIONS: An evidence-based decision aid was developed to support parents of children with cancer in making decisions about CAM for pain management. Next steps will be to expand the website to include additional childhood cancer-related complaints and to evaluate its use in practice.

Systems Health: A Transition from Disease Management Toward Health Promotion.

To date, most of the chronic diseases such as cancer, cardiovascular disease, and diabetes, are the leading cause of death. Current strategies toward disease treatment, e.g., risk prediction and target therapy, still have limitations for precision medicine due to the dynamic and complex nature of health. Interactions among genetics, lifestyle, and surrounding environments have nonnegligible effects on disease evolution. Thus a transition in health-care area is urgently needed to address the hysteresis of diagnosis and stabilize the increasing health-care costs. In this chapter, we explored new insights in the field of health promotion and introduced the integration of systems theories with health science and clinical practice. On the basis of systems biology and systems medicine, a novel concept called "systems health" was comprehensively advocated. Two types of bioinformatics models, i.e., causal loop diagram and quantitative model, were selected as examples for further illumination. Translational applications of these models in systems health were sequentially discussed. Moreover, we highlighted the bridging of ancient and modern views toward health and put forward a proposition for citizen science and citizen empowerment in health promotion.

Metabolomics profiling of the free and total oxidised lipids in urine by LC-MS/MS: application in patients with rheumatoid arthritis.

Oxidised lipids, covering enzymatic and auto-oxidation-synthesised mediators, are important signalling metabolites in inflammation while also providing a readout for oxidative stress, both of which are prominent physiological processes in a plethora of diseases. Excretion of these metabolites via urine is enhanced through the phase-II conjugation with glucuronic acid, resulting in increased hydrophilicity of these lipid mediators. Here, we developed a bovine liver-ß-glucuronidase hydrolysing sample preparation method, using liquid chromatography coupled to tandem mass spectrometry to analyse the total urinary oxidised lipid profile including the prostaglandins, isoprostanes, dihydroxy-fatty acids, hydroxy-fatty acids and the nitro-fatty acids. Our method detected more than 70 oxidised lipids biosynthesised from two non-enzymatic and three enzymatic pathways in urine samples. The total oxidised lipid profiling method was developed and validated for human urine and was demonstrated for urine samples from patients with rheumatoid arthritis. Pro-inflammatory mediators PGF2α and PGF3α and oxidative stress markers iPF2α- IV, 11-HETE and 14-HDoHE were positively associated with improvement of disease activity score. Furthermore, the anti-inflammatory nitro-fatty acids were negatively associated with baseline disease activity. In conclusion, the developed methodology expands the current metabolic profiling of oxidised lipids in urine, and its application will enhance our understanding of the role these bioactive metabolites play in health and disease.

Delayed luminescence: an experimental protocol for Chinese herbal medicines.

In Chinese medicine, raw herbal materials are used in processed and unprocessed forms aiming to meet the different requirements of clinical practice. To assure the chemical quality and therapeutic properties of the herbs, fast and integrated systematic assays are required. So far, such assays have not been established. Delayed luminescence (DL) refers to a decaying long-term ultraweak photon emission after exposure to light. Its decay kinetics under certain conditions may be a sensitive indicator reflecting the internal structural and chemical/physiological state of a biological system. DL measurements have been used in many applications for quality control. However, relatively little research has been reported on dried plant material such as Chinese herbs. The objective of the present study is to establish a protocol for direct and rapid DL measurements of dried Chinese herbal materials, including the determination of the dependence on: (a) the optimal excitation time utilizing a white light source; (b) the optimal size of the grinded herbal particle; and (c) the humidity conditions before and during measurement. Results indicate that stable and reproducible curves of DL photon emission depend mainly on the water content of herbal materials. To investigate the application of the established DL measurement protocol, non-processed and processed Aconitum (Aconitum carmichaelii Debx.), wild and cultivated rhubarb (Rheum palmatum L.) and ginseng (Panax ginseng C.A.Mey) of different ages were measured using DL. The results suggest that DL technology is a potential tool for assessment of dried Chinese herb qualities. The results warrant a further exploration of this technique in relation to therapeutic properties of the herbs. Copyright © 2016 John Wiley & Sons, Ltd.

Differences between serum polar lipid profiles of male and female rheumatoid arthritis patients in response to glucocorticoid treatment.

OBJECTIVE: As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients. METHODS: Serum samples from 281 RA patients were analysed using a targeted lipidomics platform. The differences in GC use and gender on polar lipid profiles were cross sectionally examined by multiple linear regressions, while correcting for confounding factors. RESULTS: Differences in polar lipids between GC users and non-GC users in females and males were merely restricted to lysophospholipids (lysophosphatidylcholines and lysophosphatidylethanolamines). Lysophospholipids in female patients treated with GCs were significantly higher than female patients not treated with GCs (p = 6.0 E-6), whereas no significant difference was observed in male GC users versus non-users (p = 0.397). CONCLUSION: The lysophospholipid profiles in response to GCs were significantly different between male and female RA patients, which may have implications for the cardiovascular risk of GC treatment.

Collagen Induced Arthritis in DBA/1J Mice Associates with Oxylipin Changes in Plasma.

Oxylipins play important roles in various biological processes and are considered as mediators of inflammation for a wide range of diseases such as rheumatoid arthritis (RA). The purpose of this research was to study differences in oxylipin levels between a widely used collagen induced arthritis (CIA) mice model and healthy control (Ctrl) mice. DBA/1J male mice (age: 6-7 weeks) were selected and randomly divided into two groups, namely, a CIA and a Ctrl group. The CIA mice were injected intraperitoneally (i.p.) with the joint cartilage component collagen type II (CII) and an adjuvant injection of lipopolysaccharide (LPS). Oxylipin metabolites were extracted from plasma for each individual sample using solid phase extraction (SPE) and were detected with high performance liquid chromatography/tandem mass spectrometry (HPLC-ESI-MS/MS), using dynamic multiple reaction monitoring (dMRM). Both univariate and multivariate statistical analyses were applied. The results in univariate Student's t-test revealed 10 significantly up- or downregulated oxylipins in CIA mice, which were supplemented by another 6 additional oxylipins, contributing to group clustering upon multivariate analysis. The dysregulation of these oxylipins revealed the presence of ROS-generated oxylipins and an increase of inflammation in CIA mice. The results also suggested that the collagen induced arthritis might associate with dysregulation of apoptosis, possibly inhibited by activated NF-κB because of insufficient PPAR-γ ligands.

Looking back into the future: 30 years of metabolomics at TNO.

Metabolites have played an essential role in our understanding of life, health, and disease for thousands of years. This domain became much more important after the concept of metabolism was discovered. In the 1950s, mass spectrometry was coupled to chromatography and made the technique more application-oriented and allowed the development of new profiling technologies. Since 1980, TNO has performed system-based metabolic profiling of body fluids, and combined with pattern recognition has led to many discoveries and contributed to the field known as metabolomics and systems biology. This review describes the development of related concepts and applications at TNO in the biomedical, pharmaceutical, nutritional, and microbiological fields, and provides an outlook for the future.

Two-Year Results of a Five-Year Personalized Integrative Obesity Coaching Program (IBO) Based upon a Systems Health Perspective and an Evolutionary Longitudinal Study Approach.

This study presents the outcomes of a 5-year personalized integrative coaching program for adults with obesity (body mass index BMI ≥ 30 kg/m2), based upon a systems health perspective, during the first 2 years. This longitudinal study, which had an evolutionary design, included all adults who enrolled in the program. Health-related quality of life (HRQoL) was measured with the Short Form-36 (SF-36), and physical outcomes included weight, waist circumference, aerobic capacity, lipid profile, and HbA1c. Subsequently, participants completed questionnaires (e.g., the Symptom Checlist-90 (SCL-90) and the Checklist Individual Strength (CIS)). Seventy-nine adults with a mean BMI of 39.5 kg/m2 (SD 5.3) were included. Forty-four participants completed 2 years in the program. Compared to baseline, there were significant improvements in the SF-36 subscales 'physical functioning' (MD 9.9 points, 95% CI: 2.1-17.5, p = 0.013) and 'general health perceptions' (MD 9.3 points, 95% CI 2.9-15.7, p = 0.006). Furthermore, significant improvements in physical outcomes and psychosocial questionnaires (e.g., weight loss (MD 3.5 kg, 95% CI: 1.2-5.7, p = 0.003), waist circumference (MD 5.1 cm, 95% CI: 2.4-7.8, p < 0.001), and CIS fatigue (MD 6.8, 95% CI: 3.1-10.5, p = 0.001) were observed. This study highlights the importance of a systems health perspective supporting the development of a personalized integrative coaching program for adults with obesity in a 'real-world' setting.

The Use of the Bolk Model for Positive Health and Living Environment in the Development of an Integrated Health Promotion Approach: A Case Study in a Socioeconomically Deprived Neighborhood in The Netherlands.

BACKGROUND: Despite considerable efforts, health disparities between people with high and low socioeconomic status (SES) have not changed over the past decades in The Netherlands. To create a culture of health and an environment in which all people can flourish, a shift in focus is needed from disease management towards health promotion. The Bolk model for Positive Health and Living Environment was used as a tool to guide this shift. This study aimed to describe how this model was used and perceived by stakeholders in a case study on an integrated health promotion approach for residents with low SES. METHODS: An instrumental case study was undertaken in Venserpolder, a neighborhood in Amsterdam South East of approximately 8500 residents. A participatory action approach was used that allowed continuous interaction between the residents, health care professionals, researchers, and other stakeholders. The Bolk model is a tool, based on the conceptual framework of positive health, that was developed to guide health promotion practice. Its use in the case study was evaluated by means of semistructured interviews with stakeholders, using qualitative directed content analyses. RESULTS: The Bolk model was found to be a useful tool to identify and map the needs and strengths of residents with low SES. The model facilitated the development and implementation of eight health promotion pilots by transforming the needs and strengths of residents into concrete actions carried out by responsible actors in the neighborhood. Although the Bolk model seemed to be accepted by all stakeholders, the shift towards positive health thinking appeared to be more embodied by local professionals than by residents. Adjustments were proposed to enhance the applicability of the model in a multicultural setting, to increase its cultural sensitivity and to use language more familiar to residents. CONCLUSIONS: The Bolk model for positive health and living environment seems to be promising in the guidance of health promotion practices in Amsterdam South East. Further research and development are needed to improve its cultural sensitivity and to investigate its applicability in a broader range of public health settings.

Effectiveness of herbal medicines to prevent and control symptoms of urinary tract infections and to reduce antibiotic use: A literature review.

Background: Antimicrobial resistance is a rapidly growing global issue affecting the effective treatment of infectious diseases. This provides a window of opportunity for the use and implementation of well researched effective complementary therapies such as herbal medicines. In this literature review, an overview is provided of the effectiveness of herbal medicine to control symptoms of urinary tract infections and reduce antibiotic use. Methods: PubMed, CAM-Quest, CORE-Hom, ScienceDirect, CAMBase, Anthromedics.org and AnthroMedLibrary databases were searched for peer-reviewed meta-analyses, systematic reviews and randomized controlled trials from 2005 till 8 October 2020. Included were clinical studies on the use of herbal medicine for clinically diagnosed urinary tract infection with any control group except another herbal medicine. Study quality was assessed using the Joanna Briggs Institute critical appraisal tools. Results: Of the 408 citations identified, 23 met the inclusion criteria: 5 meta-analyses, 3 systematic reviews and 15 randomized controlled trials. Of these studies 13 involved the use of cranberry products, 4 studies concerned traditional Chinese herbal medicines, and 6 studies dealt with other herbal medicines. Conclusions: The latest published meta-analysis including 28 trials reports a clear benefit of Cranberry products for the prevention of recurrent UTIs in women. Five TCM formulas were found to be equally or more effective than antibiotics in the treatment of UTIs. Furthermore, Rosa canina seems to have the potential to prevent UTI in women undergoing a caesarean section. 'Acidif Plus Tablets' as well as 'Canephron' seem to be promising candidates for treating women with uncomplicated recurrent UTI.

Sparse System Identification of Leptin Dynamics in Women With Obesity.

The prevalence of obesity is increasing around the world at an alarming rate. The interplay of the hormone leptin with the hypothalamus-pituitary-adrenal axis plays an important role in regulating energy balance, thereby contributing to obesity. This study presents a mathematical model, which describes hormonal behavior leading to an energy abnormal equilibrium that contributes to obesity. To this end, we analyze the behavior of two neuroendocrine hormones, leptin and cortisol, in a cohort of women with obesity, with simplified minimal state-space modeling. Using a system theoretic approach, coordinate descent method, and sparse recovery, we deconvolved the serum leptin-cortisol levels. Accordingly, we estimate the secretion patterns, timings, amplitudes, number of underlying pulses, infusion, and clearance rates of hormones in eighteen premenopausal women with obesity. Our results show that minimal state-space model was able to successfully capture the leptin and cortisol sparse dynamics with the multiple correlation coefficients greater than 0.83 and 0.87, respectively. Furthermore, the Granger causality test demonstrated a negative prospective predictive relationship between leptin and cortisol, 14 of 18 women. These results indicate that increases in cortisol are prospectively associated with reductions in leptin and vice versa, suggesting a bidirectional negative inhibitory relationship. As dysregulation of leptin may result in an abnormality in satiety and thereby associated to obesity, the investigation of leptin-cortisol sparse dynamics may offer a better diagnostic methodology to improve better treatments plans for individuals with obesity.

Developing a Personalized Integrative Obesity-Coaching Program: A Systems Health Perspective.

Current obesity management strategies are failing to achieve sustainable and favorable long-term results. We propose a more personalized, dynamic, and systemic perspective on the interactions of key determinants and coaching advice on obesity. The aim of this study was to use a systems view on overweight, complexity science, and a transdisciplinary process to develop a five-year personalized integrative obesity-coaching and research program. Managers, medical specialists, clinical psychologists, dieticians, physical- and psychomotor therapists, and lifestyle coaches aligned their perspectives and objectives with experts in systems thinking and systems biology. A systems health model of obesity was used to identify the causal relations of variables with the most influence on obesity. The model helped to align and design a personalized integrative obesity-coaching program and to identify the key variables to monitor the progress and to adjust the personalized program, depending on the goals and needs of the participant. It was decided to use subtyping of participants by a systems biologist, based on traditional Chinese medicine symptoms, as a novel method to personalize the intervention. The collaborative transdisciplinary approach based upon a systems view on obesity was successful in developing a personalized and adaptive five-year obesity-coaching and research program.

Corrigendum: Sparse system identification of leptin dynamics in women with obesity.

[This corrects the article DOI: 10.3389/fendo.2022.769951.].

Anthroposophic Medicinal Products: A Literature Review of Features, Similarities and Differences to Conventional Medicinal Products, Scientific and Regulatory Assessment.

Background: Regulatory assessment of anthroposophic medicinal products (AMPs) can be challenging due to their specific features. Objective: The aim of this paper is therefore to provide adequate scientific information on AMPs for regulatory purposes. Methods: A literature review was executed with database searches in PubMed, Cinahl, Merkurstab, Anthromedics, and https://iaap-pharma.org/. Search terms were: anthroposophic medicinal products, anthroposophic medicines, anthroposophic pharmacy. There was no language restriction; searches were executed from onset until June 11, 2020. In addition, experts were invited to suggest relevant literature. Results: Eighty-seven of 660 identified publications were included. The system of anthroposophic medicine (AM) with its conceptual background and various aspects of AMPs was described: definition, pharmaceutical properties, an example of AMP development, use in clinical practice, similarities with and differences to conventional medicinal products, societal aspects, scientific and regulatory assessment. Conclusion: AMPs are part of the integrative whole medical system of AM. AMPs are manufactured according to Good Manufacturing Practice and national drug regulations and have an excellent safety status; the limited available evidence suggests clinical benefits. Current drug regulation of AMPs in the EU and most European countries does not take the special properties of AMPs into account. Future research should focus on appropriate methodologies for the evaluation of effects of AMPs as part of the AM whole medical system, the scientific quality of its non-atomistic holistic ontological position, and the integration of AM and conventional medicine in clinical practice. Future policies should focus on appropriate ways of addressing regulatory challenges to AMPs.

Complementary Medicine and Self-Care Strategies in Women with (Recurrent) Urinary Tract and Vaginal Infections: A Cross-Sectional Study on Use and Perceived Effectiveness in The Netherlands.

Due to the excessive use of antibiotic and antimycotic treatments, the risk of resistant microbes and fungi is rapidly emerging. Previous studies have demonstrated that many women with (recurrent) urinary tract infection (UTI) and/or vaginal infections (VIs) welcome alternative management approaches to reduce the use of antibiotics and antifungals and avoid short- and long-term adverse effects. This study aims to determine which complementary medicine (CM) and self-care strategies are being used by women suffering from (recurrent) UTI and VI in The Netherlands and how they perceive their effectiveness in order to define directions for future research on safety, cost-effectiveness, and implementation of best practices. A cross-sectional online survey was performed among women, ≥18 years old, with a history of UTIs; 162 respondents were included in the data analysis, with most participants aged between 50 and 64 years (36.4%). The women reported having consulted a CM practitioner for UTI-specific symptoms (23.5%) and VI-specific symptoms (13.6%). Consultations of homeopaths, acupuncturists, and herbal physicians are most often reported. Overall, 81.7% of the women suffering from UTI used complementary or self-care strategies besides regular treatment, and 68.7% reported using CM/self-care strategies to treat vaginal symptoms. UTI- related use of cranberries (51.9%), vitamin C (43.8%), and D-mannose (32.7%) were most reported. Perceived effectiveness was mostly reported for homeopathic remedies and D-mannose. The results showed a substantial burden of UTI and VI on daily and sexual activities. Besides the frequency of use, the indication of perceived effectiveness seems to be an important parameter for further and rigorously designed research to encourage nonantibiotic/antifungal treatment implementation into daily clinical practice.

Safety of Anthroposophic Medicinal Products: An Analysis of Adverse Drug Reactions from German Pharmacovigilance Databases.

BACKGROUND: Anthroposophic medicinal products (AMPs) are widely used in Europe and world-wide. OBJECTIVE: To determine the frequency of reported adverse drug reactions (ADRs) from all AMPs on the market, in absolute numbers and relative to the maximum daily administration doses (MDADs). PATIENTS AND METHODS: Retrolective safety analysis of AMP-related ADRs in pharmacovigilance databases of four AMP Marketing Authorisation Holders in Germany. For each ADR, information about the patient, outcome, causality and AMP was retrieved. Primary outcome was the frequency of reported ADRs relative to MDADs sold. RESULTS: In the period 2010-2017, a total of 5506 ADRs were reported that had occurred in 2765 different patients, comprising 370 different AMPs. A total of 104 ADRs (1.9%) were classified as serious. The frequency of ADRs for all AMPs was 1.50 per million MDADs. For serious ADRs the frequency was 0.03 per million MDADs. ADRs were more frequently reported with parenteral AMP administration (injections) than with oral or local administration (18.85 vs. 0.59 vs. 1.61 ADRs per million MDADs, respectively; p < 0.0001). The large majority of users (91.9%) had recovered or were recovering from the ADRs and there were no reports with a fatal outcome. Most frequently reported ADR symptom was injection site inflammation for parenteral AMPs (4.66 ADRs per million MDADs), nausea for oral AMPs (0.03 ADRs per million MDADs), and eye irritation for locally administered AMPs (0.23 ADRs per million MDADs). CONCLUSIONS: In this retrolective safety analysis of pharmacovigilance data, the frequency of ADRs to AMPs was 1.50 per million MDADs. Notably, the ADR frequency in this study based on spontaneous reporting is not directly comparable to frequencies in prospective clinical studies nor to frequencies based on other measures of patient exposure than MDADs.

Systems biology-based diagnostic principles as pillars of the bridge between Chinese and Western medicine.

Innovative systems approaches to develop medicine and health care are emerging from the integration of Chinese and Western medicine strategies, philosophies and practices. The two medical systems are highly complementary as the reductionist aspects of Western medicine are favourable in acute disease situations and the holistic aspects of Chinese medicine offer more opportunities in chronic conditions and for prevention. In this article we argue that diagnosis plays a key role in building the bridge between Chinese and Western medicine. Recent advances in the study of health, healing, placebo effects and patient-physician interactions will be discussed pointing out the development of a system-based diagnosis. Especially, a system biology-based diagnosis can be used to capture phenotype information, leading towards a scientific basis for a more refined patient characterization, new diagnostic tools and personalized heath strategies. Subtyping of rheumatoid arthritis patients based on Chinese diagnostic principles is discussed as an example. New insights from this process of integrating Western and Chinese medicine will pave the way for a patient-centred health care ecosystem.

Corrigendum to "The Contribution of Complementary and Alternative Medicine to Reduce Antibiotic Use: A Narrative Review of Health Concepts, Prevention, and Treatment Strategies".

[This corrects the article DOI: 10.1155/2019/5365608.].

Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients.

BACKGROUND: Complex chronic diseases such as rheumatoid arthritis have become a major challenge in medicine and for the pharmaceutical industry. New impulses for drug development are needed. OBJECTIVE: : A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized medicine. METHODS: Blood samples of 33 rheumatoid arthritis (RA) patients and 16 healthy volunteers were collected. The RA patients were diagnosed according to Chinese medicine (CM) theory and divided into 2 groups, the RA Heat and RA Cold group. CD4 T-cells were used for a total gene expression analysis. Metabolite profiles were measured in plasma using gas chromatography/mass spectrometry. Multivariate statistics was employed to find potential biomarkers for the RA Heat and RA Cold phenotype. A comprehensive biologic interpretation of the results is discussed. RESULTS: : The genomics and metabolomics analysis showed statistically relevant different gene expression and metabolite profiles between healthy controls and RA patients as well as between the RA Heat and RA Cold group. Differences were found in the regulation of apoptosis. In the RA Heat group caspase 8 activated apoptosis seems to be stimulated while in the RA Cold group apoptosis seems to be suppressed through the Nrf2 pathway. CONCLUSIONS: RA patients could be divided in 2 groups according to CM theory. Molecular differences between the RA Cold and RA Heat groups were found which suggest differences in apoptotic activity. Subgrouping of patients according to CM diagnosis has the potential to provide opportunities for better treatment outcomes by targeting Western or CM treatment to specific groups of patients.