Integrative medicine for hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS): a feasibility study.

PURPOSE: Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are multisystem conditions marked by dysfunctional connective tissue. This feasibility study evaluated a 9-week integrative medicine program in this population. METHODS: Using a single-arm study design, adults with HSD or EDS were given recommendations for an anti-inflammatory Mediterranean diet and self-management with additional behavioral and psychosocial support. Preliminary data on feasibility based on recruitment and retention, adherence to the diet, mobile app tracking, changes to perceived well-being via health outcomes, and satisfaction with care were obtained. RESULTS: Thirteen participants were enrolled within a 4-month timeframe. Eight participants completed the study. Three participants met dietary tracking requirement in at least 4 of 8 intervention weeks and met the macronutrient requirements in at least half of the weeks tracked. No decreases in VAS pain scores after 5 and 9 weeks were noted; however, 62.5% (n = 5) of participants had decreased pain at 9 weeks, compared to baseline. There were significant improvements (p<.05) in six of twelve measurements of satisfaction with care at the end of the intervention. CONCLUSION: This study provides a foundation for future research on patient experience and introduces a novel treatment paradigm focused on nutrition and self-management.Trial Registration: National Institutes of Health clinicaltrials.gov; identifier: NCT04734041. IMPLICATIONS FOR REHABILITATION: Lifestyle and dietary interventions are relatively safe and well tolerated in the hypermobility spectrum disorder (HSD) and Ehlers-Danlos disorder (EDS) population.Participants in our 9-week integrative medicine program actively engaged in self-management of their condition and showed promising adherence to dietary and tracking requirements.Effective treatment of the intricacies and dynamics of these highly variable and clinically heterogeneous disorders may require a network of healthcare providers, integrative healthcare, as well as behavioral and psychosocial support.Dietary tracking through mobile apps might help promote self-efficacy and adherence to dietary changes.Symptom tracking might be an effective way for patients to track changes to their health and could provide valuable information for health professionals engaged in managing the disorders.

Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Patient experience of chronic illness care and complementary integrative health use: a cross-sectional study of patients with hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS).

PURPOSE: Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are frequently underdiagnosed, contributing to patient dissatisfaction in the healthcare system. This study evaluated the health service utilization, care, and subjective experiences of living with chronic illness among adults with HSD and EDS in the United States and Canada. METHODS: This was an anonymous, web-based, cross-sectional healthcare survey. The survey obtained basic demographic information, the Patient Assessment of Chronic Illness Care (PACIC+), as well as responses to questions on the use of healthcare and integrative medicine. RESULTS: A total of 353 surveys were received. The most common complementary therapies used were physical therapy (82%), massage (68%), yoga (58%), chiropractic (48%), and meditation (43%). Mean (SD) summary PACIC and PACIC 5 As scores were 2.16 (0.77) and 2.25 (0.83), respectively. Across all PACIC domains, mean scores of individuals whose typical doctor visit was 30 min or at least an hour were significantly higher than those of individuals who indicated typical visits of 15 min (all p < 0.0001 by one-way ANOVA). There was widespread agreement on the importance of patient-provider relationship and trust, physicians' understanding of the individual's complete medical history, and prioritization of physical and emotional safety (>95% agree or strongly agree to each). CONCLUSION: Individuals with HSD or EDS report low satisfaction with chronic illness care and commonly seek out complementary and self-administered therapies, likely in an attempt to manage symptoms. Respondents reported a desire for greater time and attention from physicians. Results from this study could educate the healthcare community to improve support mechanisms for HSD and EDS populations.IMPLICATIONS FOR REHABILITATIONPatients with hypermobility spectrum disorders (HSD) or Ehlers-Danlos syndromes (EDS) express a desire for patient-centered care and peer support from other individuals with HSD or EDS.Individuals with HSD or EDS have typically seen multiple doctors for their condition and their satisfaction with chronic care, as measured by the Patient Assessment of Chronic Illness Care (PACIC+), is low.The use of various complementary and integrative health treatments, as well as specialized diets, is common in this population, and might be beneficial for symptom management.Healthcare delivery for HSD and EDS may require a multidisciplinary healthcare team, as complementary and self-care modalities are typically used in addition to physical therapy, pain medication, and other conventional care.

Xanthohumol microbiome and signature in adults with Crohn's disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial.

BACKGROUND: Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn's disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. METHODS: A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn's Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. DISCUSSION: We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD. TRIAL REGISTRATION: ClinialTrials.gov NCT04590508. Registered on October 19, 2020.

The Acupuncture and Telehealth Survey: A Cross-Sectional Survey Exploring Early COVID-19 Impacts on the Acupuncture Profession.

Introduction: As the COVID-19 pandemic continues to impact workforces in the United States, the Acupuncture and Telehealth Survey was released to assess the acupuncture profession's use of telehealth and workforce response to a changing regulatory landscape. Methods: An online cross-sectional survey of licensed acupuncturists in the United States was conducted in May 2020 for 4 weeks. Novel online recruitment strategies were successfully implemented including social media pages, digital media marketing, and webinar presentations. Statistical analyses were used to ascertain varying impacts on acupuncturists with telehealth training, and the use of online health care platforms, stratified by age, and history of licensure. Results: One thousand forty-five respondents from 46 states completed the survey. The majority of respondents noted a significant reduction in working hours regardless of telehealth training history (mean -18.7 h/week, p < 0.001, 95% confidence interval [-19.5 to -18.0]); however, acupuncturists managing patients online reported a lesser magnitude of impact (mean -17.3, p = 0.004). Respondents noted stress, immune support, and pain as the most common conditions managed through telehealth. Acupuncturists using telehealth primarily educated patients on nutrition- or herbal-based therapies and acupressure techniques, similar to acupuncturists managing suspected or confirmed COVID-19 cases. Although only 21% of acupuncturists reported receiving telehealth training, 38% were providing telehealth, and 13% were considering it in the future with concerns for quality patient care. Discussion: Acupuncturists' working hours were significantly reduced during the COVID-19 pandemic although many pivoted to a variety of online health care techniques and profession-specific modalities for continued patient care. This effect could be minimized by the use of telehealth platforms, necessitating adequate training on telehealth in the acupuncture profession.

Inflammatory Bowel Disease and Neutrophil-Lymphocyte Ratio: A Systematic Scoping Review.

Neutrophil-lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD.

Xanthohumol Microbiome and Signature in Healthy Adults (the XMaS Trial): Safety and Tolerability Results of a Phase I Triple-Masked, Placebo-Controlled Clinical Trial.

SCOPE: Xanthohumol, a prenylflavonoid from hops, has been extensively studied preclinically but has undergone limited research in human subjects. A triple-masked, placebo-controlled phase I clinical trial was conducted to examine the safety and tolerability of xanthohumol. METHODS AND RESULTS: Thirty healthy volunteers were randomized to 24 mg day-1 xanthohumol (99.8% pure) or placebo for eight weeks. Comprehensive metabolic panels, complete blood counts, body weight, vital signs, and health-related quality of life questionnaires were assessed every two weeks. Participants were interviewed for adverse events (AEs) throughout the trial. Thirteen of 14 (93%) and 14 of 16 (88%) participants completed the trial in the placebo and xanthohumol groups, respectively. There were no withdrawals due to AEs. There were no clinically relevant, between-group differences in laboratory biomarkers, body weight, vital signs, or health-related quality of life. There were no severe or FDA-defined serious AEs, but non-serious AEs are documented in both the placebo (n = 42) and xanthohumol (n = 58) groups. CONCLUSION: Over an eight-week period, 24 mg daily xanthohumol was safe and well-tolerated by healthy adults.

Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial.

BACKGROUND: Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial ("XMaS") was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol's impact on gut microbial composition. METHODS: The safety and tolerability of xanthohumol in healthy adults will be evaluated in a triple-masked, randomized, placebo-controlled trial. Participants will be randomized to either 24 mg/day of xanthohumol or placebo for 8 weeks. Blood cell counts, hepatic and renal function tests, electrolytes, and self-reported health-related quality of life measures will be collected every 2 weeks. Participants will be queried for adverse events throughout the trial. Xanthohumol metabolites in blood, urine, and stool will be measured. Biomarkers to be evaluated include plasma tumor necrosis factor-alpha, various interleukins, soluble CD14, lipopolysaccharide-binding protein, fecal calprotectin, and bile acids to assess impact on inflammatory and gut permeability-related mechanisms in vivo. Stool samples will be analyzed to determine effects on the gut microbiome. DISCUSSION: This phase I clinical trial of xanthohumol will assess safety and tolerability in healthy adults, collect extensive biomarker data for assessment of potential mechanism(s), and provide comparison data necessary for future phase II trials in chronic disease(s). The design and robustness of the planned safety and mechanistic evaluations planned provide a model for drug discovery pursuits from natural products. TRIAL REGISTRATION: ClinicalTrials.gov NCT03735420 . Registered on November 8, 2018.

Correction to: Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial.

An amendment to this paper has been published and can be accessed via the original article.