Acupuncture improves chemotherapy-induced neuropathy explored by neurophysiological and clinical outcomes - The randomized, controlled, cross-over ACUCIN trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is recognized as the second commonest side effect after chemotherapy. Besides neurological deficits and pain, it is a potential reason for terminating chemotherapy. Effective curative treatments of neurodegeneration are lacking. Hitherto, no randomized controlled study used nerve conduction studies (NCS), the gold standard diagnostic tool for peripheral neuropathy, as the primary outcome parameter for evaluating acupuncture for CIPN, which can also measure structural changes. METHODS: The study was carried out at the HanseMerkur Center for TCM at the University Medical Center, Hamburg-Eppendorf. Sixty patients with CIPN were included in the study after physical examination, subjective evaluation and quantitative evaluation by NCS. Subsequently, the patients were randomly assigned to Group 1 (30 patients), which received, in the first period, needle acupuncture and to Group 2 (30 patients), which was assigned to the waiting list in the first period. Group 1 received a standard 10-week bilateral treatment of ST34 (Liangqiu), EX-LE12 (Qiduan) and EX-LE8 (Bafeng). After 14 weeks, both groups were re-evaluated. Using a cross-over design, the patients of Group 2 received the same treatment procedure as Group 1 in the first period. Patients of Group 1 were assigned to the waiting list for the second period. After 28 weeks both groups were re-evaluated. Wilcoxon test was used as a pre-test to rule out carryover effects and to test for differences between acupuncture and the waiting list. Group assignment was not exposed to the statistician and the neurologist. RESULTS: Sural sensory nerve amplitude, and sural nerve conduction velocity, were significantly improved (p < 0.01, effect size (f) 0.55 and 0.49) compared to measurements in the waiting period. Change of NCS of the tibial nerve did not significantly differ in group comparison. Patients reported subjective improvement during acupuncture treatment superior to the waiting period for burning pain, cramps, numbness, frequency of symptoms (all p < 0.01) and unsteadiness of gait (p < 0.05). On physical examination, blind walking, heel-to-toe walking, distal pallhypesthesia (both p < 0.01), and the neuropathy deficit score (p < 0.05) were significantly improved during acupuncture treatment compared to the waiting period. CONCLUSION: Acupuncture can enhance structural regeneration in CIPN as measured by NCS, which is manifested in subjective improvement and neurological findings.

Naturopathy, complementary and integrative medicine in medical education - position paper by the GMA Committee Integrative Medicine and Perspective Pluralism.

Background: A large part of the population in Germany makes use of naturopathic, complementary and integrative medical treatments. There are now numerous scientific studies that provide evidence of efficacy for certain indications. At German medical faculties, selected procedures and their application are taught within the cross-sectoral unit called QB 12 and some elective courses, with a focus on specific aspects are offered. So far, however, there has been no structured curriculum that longitudinally anchors teaching across medical studies and enables all students to consider naturopathic and complementary medical options for patient care later on and to integrate them effectively into the diagnostic and treatment process. Objective: The aim of this position paper is to show the relevance of this topic for medical education, to clarify terminology and to present core competencies and possible implementation options for training. Method: The Integrative Medicine and Perspective Pluralism Committee of the German Association for Medical Education developed this position paper in a multi-stage consensual process, in cooperation with the Forum of University Work Groups on Naturopathic Treatment and Complementary Medicine. Results: First, different umbrella terms were discussed and an existing definition of integrative medicine and health was chosen for subsequent use. Building on this step, the status of education and its scientific foundation in Germany was considered in an international context. In the next step, a competency profile for medical training, consisting of seven areas of competency, was developed and described in detail with regard to naturopathic, complementary and integrative medicine. Implementation options were identified using possible starting points in the curriculum and using established examples of best practice. Conclusion: Despite different priorities at each faculty, it was possible to find an agreement on the development of competencies and anchoring them in medical education on the basis of a common definition of terms. Currently, the implementation in the mandatory and elective areas is very heterogeneous. As part of the current revision of the Medical Licensure Act, there are many possible starting points for the integration of naturopathic and complementary medical teaching content, especially in interprofessional and general practice courses. The implementation and accompanying research of targeted teaching settings should lay the foundations for a long-term and binding integration into medical education. Overall, it is clear that medical education in the field of naturopathy and complementary and integrative medicine has the potential to develop comprehensive core medical competencies.

Experiences and views of different key stakeholders on the feasibility of treating cancer-related fatigue.

BACKGROUND: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, therapy remains a challenge. Treatment programs are more likely to be effective if the needs and interests of the persons involved are well represented. This can be achieved by stakeholder engagement. In this paper, different key stakeholders' experiences and views on the feasibility of treating CRF in the context of supportive care in hospital environments are analyzed. METHOD: In a qualitative study with the aim of developing an integrative treatment program for CRF, a total of 22 stakeholders (6 medical oncologists, 5 nurses, 9 patients, 1 patient family member, 1 representative of the Swiss Cancer League) were interviewed either in a face-to-face (n = 12) or focus group setting (n = 2). For data analyses, the method of qualitative content analysis was used. RESULTS: The stakeholders referred to different contextual factors when talking about the feasibility of treating CRF in the context of supportive care in hospital environments. These included: assessment, reporting and information; treatability; attitude; infrastructure, time-management, costs and affordability; and integrative approach. CONCLUSIONS: Key factors of a feasible treatment approach to CRF are a coherent, cost effective integrative treatment program facilitated by an interdisciplinary team of health care providers. Furthermore, the treatment approach should be patient orientated, adopting an individualized approach. The major challenges of making the integrative treatment program feasible for CRF are resources and interprofessional collaboration.

[Mistletoe in the treatment of cancer patients]. / Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung.

Mistletoe (Viscum album L.) continues to be the medical herb prescribed most frequently for cancer patients in German-speaking countries. Demand for this therapy often comes from patients themselves and requires careful consideration by the attending physician during consultation.In German-speaking countries, mistletoe extracts are available as approved drugs (based on monographs of the commissions C and E of the German Federal Institute for Drugs and Medical Devices). In Switzerland, treatment costs are generally covered by statutory health insurance. In Germany, coverage is limited to palliative care. In adjuvant cases, treating physicians can request coverage by the health insurance if patients suffer from side effects due to the antitumoral treatment.The spectrum of Viscum album extract includes mistletoe lectin I; II, and III, viscotoxins, flavonoids, amino acids, polysaccharides, and membrane lipids. Preclinical studies have demonstrated cytotoxic, apoptosis-inducing, and immunomodulatory effects.Many clinical studies indicate a supportive efficacy of mistletoe extracts in tumor patients, even though methodological quality is discussed controversially in many cases. Clinical data regarding effects on survival of patients is inconsistent; effects concerning quality of life as well as the tolerability of antitumoral treatments are evaluated more positively.In view of the high demand on the patient side and increasing scientific evidence, the general conditions for prescriptions should continue as well as the ongoing scientific evaluation.

Developing an Integrative Treatment Program for Cancer-Related Fatigue Using Stakeholder Engagement - A Qualitative Study.

BACKGROUND: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, it remains difficult to treat. An integrative approach combining conventional and complementary medicine interventions seems highly promising. Treatment programs are more likely to be effective if the needs and interests of the people involved are well represented. This can be achieved through stakeholder engagement. OBJECTIVES: The aim of the study was to develop an integrative CRF treatment program using stakeholder engagement and to compare it to an expert version. METHOD: In a qualitative study, a total of 22 stakeholders (4 oncologists, 1 radiation-oncologist, 1 psycho-oncologist, 5 nurses/nurse experts, 9 patients, 1 patient family member, 1 representative of a local Swiss Cancer League) were interviewed either face-to-face or in a focus group setting. For data analysis, qualitative content analysis was used. RESULTS: With stakeholder engagement, the integrative CRF treatment program was adapted to usual care using a prioritizing approach and allowing more patient choice. Unlike the expert version, in which all intervention options were on the same level, the stakeholder engagement process resulted in a program with 3 different levels. The first level includes mandatory nonpharmacological interventions, the second includes nonpharmacological choice-based interventions, and the third includes pharmacological interventions for severe CRF. The resulting stakeholder based integrative CRF treatment program was implemented as clinical practice guideline at our clinic (Institute for Complementary and Integrative Medicine, University Hospital Zurich). CONCLUSION: Through the stakeholder engagement approach, we integrated the needs and preferences of people who are directly affected by CRF. This resulted in an integrative CRF treatment program with graded recommendations for interventions and therefore potentially greater sustainability in a usual care setting.

Alteration of anti-inflammatory activity of Harpagophytum procumbens (devil's claw) extract after external metabolic activation with S9 mix.

OBJECTIVES: Extracts of the tubers of Harpagophytum procumbens (devil's claw, DC) inhibit different proinflammatory mediators important in the pathophysiology of osteoarthritis. Many plant-derived preparations interfere with cytochrome P450 liver enzymes, which influence their different biological activities. Therefore, the present study was designed to investigate the influence of an external metabolic activation of a DC extract on the cytotoxicity and the release of proinflammatory cytokines. METHODS: A screening experiment with a panel of 12 inflammatory cytokines identified three as suitable for the study: tumour necrosis factor-α (TNF-α), interleukin (IL) IL-6 and IL-8. They were determined using enzyme-linked immunosorbent assays in lipopolysaccharide (LPS)-stimulated monocytic THP-1 cells, which were treated with rat liver S9 mix metabolically activated DC extract (DCm). For the cytotoxity experiments, a WST-1 assay was used. KEY FINDINGS: DC dose-dependently suppressed the release of TNF-α, IL-6 and IL-8 in LPS-stimulated monocytic THP-1 cells at non-cytotoxic concentrations (50-250 µg/ml). The metabolic activation of the DC extract by S9 mix did not alternate its cytotoxicity and did not diminish its inhibitory effect. This effect was improved in the case of TNF-α inhibition as reflected by their EC50 values of 116 ± 8.2 µg/ml and 49 ± 3.5 µg/ml for DC and DCm (P < 0.01). CONCLUSIONS: Cytokines inhibitory activity of DC was not affected after its external metabolic activation. However, the amount of harpagoside and caffeic acid derivates was decreased. Other components of the extract might have contributed to its anti-inflammatory effect.

A survey of chinese medicinal herbal treatment for chemotherapy-induced oral mucositis.

Oral mucositis is one of the common side effects of chemotherapy treatment with potentially severe implications. Despite several treatment approaches by conventional and complementary western medicine, the therapeutic outcome is often not satisfactory. Traditional Chinese Medicine (TCM) offers empirical herbal formulas for the treatment of oral ulceration which are used in adaptation to chemotherapy-induced mucositis. While standard concepts for TCM treatment do not exist and acceptance by conventional oncologists is still low, we conducted a review to examine the evidence of Chinese herbal treatment in oral mucositis. Eighteen relevant studies on 4 single herbs, 2 combinations of 2 herbs, and 11 multiherbal prescriptions involving 3 or more compounds were included. Corresponding molecular mechanisms were investigated. The knowledge about detailed herbal mechanisms, especially in multi-herbal prescriptions is still limited. The quality of clinical trials needs further improvement. Meta-analysis on the existent database is not possible but molecular findings on Chinese medicinal herbs indicate that further research is still promising for the treatment of chemotherapy-induced oral mucositis.

Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy?

Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan), Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto), Huang Qi Wu Wu Tang (Ogikeishigomotsuto), and Shao Yao Gan Cao Tang (Shakuyakukanzoto). The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.

A homeopathic remedy from arnica, marigold, St. John's wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts.

BACKGROUND: Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. METHODS: We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712-2), its succussed hydroalcoholic solvent (0712-1) and unsuccussed solvent (0712-3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined "wound field". All assays were performed in three independent controlled experiments. RESULTS: None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712-2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712-1) at 1:100 dilutions (p < 0.001). Unsuccussed solvent (0712-3) had no influence on cell migration (6.3%; p > 0.05). Preparation (0712-2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712-1), which caused 22.1% wound closure. CONCLUSION: Results of this study showed that the low potency homeopathic remedy (0712-2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis.

An exploratory study on the quality of life and individual coping of cancer patients during mistletoe therapy.

BACKGROUND: Although several clinical studies have shown that mistletoe therapy (MT, Viscum album) may improve cancer patients' quality-of-life (QoL), qualitative information on the improvement's nature is still lacking. DESIGN: This exploratory, prospective, cohort-study comprised 25 patients with different types of cancer. The patients filled in the EORTC QLQ-C30 Version 3.0 questionnaire at the beginning of MT (n = 25) and three months later (n = 21). If patients agreed, they were interviewed on both occasions (n = 17); the interviews were transcribed verbatim and submitted to a qualitative content analysis (n = 12). RESULTS: Analysis of the questionnaires showed significant improvements in several subscales during MT. The interviews analysis revealed that most patients adopted the MT with a supportive goal, with all patients undergoing conventional therapies. After three months of MT, most interviewed patients revealed higher vitality and autonomy. MT was often seen as a chance to make an own personal contribution to the therapy, which was particularly appreciated in cases in which no conventional therapy was (anymore) advised. Concrete personal achievements such as changes in the private and/or in the professional environment were spontaneously mentioned by the patients, illustrating and corroborating their improvements in QoL. CONCLUSION: Our results show that the patients experienced an improvement of QoL during MT. This therapy seemed to offer a platform for an integrative coping with the disease, which might be important in reconciling the perceived shock of an existential illness with a good QoL.

Phytodolor® in musculoskeletal disorders: re-analysis and meta-analysis.

BACKGROUND: Treatment of rheumatic or musculoskeletal disorders (MD) is multi-disciplinary and includes herbal analgesics. Although already reviewed, no quantitative evaluation of efficacy and safety of the herbal combination Phytodolor® (STW1) is available. METHODS: We searched in databases and contacted authors and the manufacturer to identify randomized controlled trials (RCTs) examining STW1 in patients with MD. We made a reanalysis of raw data of eligible published and unpublished RCTs and pooled the results for meta-analysis according to Cochrane guidelines and intention-to-treat. Primary outcome measure was patient global assessment of efficacy, secondary outcome measure was pain at rest and on movement. Results were stratified according to treatment groups. RESULTS: Patient data of 11 RCTs were eligible for pooling. In the entire population, STW1 was significantly superior compared to placebo in patients' global assessment of efficacy (group difference for rating very good/good: 20%; placebo 48.9% and STW1 69.1%; p < 0.001; OR 0.43; 95% CI 0.28-0.65) and in the subpopulation 'other rheumatic diseases' (placebo 45.4%; STW1 72.3%; p < 0.001; OR 0.32; 95% CI 0.2-0.52), but not in the subpopulation 'gonarthrosis'. STW1 did not differ significantly compared to non-steroidal anti-inflammatory drugs (NSAIDs), neither in the entire population nor the subpopulations. Similar results were found for pain at rest and on movement. No serious adverse events (AE) but minor AE were reported (placebo 8.1%; STW1 14.2%; NSAIDs 18.9%). CONCLUSION: According to the analysed data, STW1 showed a better pain reduction than placebo in patients with pain due to MD, probably equivalent to NSAIDs, and was well tolerated.

Classical homeopathy in the treatment of cancer patients--a prospective observational study of two independent cohorts.

BACKGROUND: Many cancer patients seek homeopathy as a complementary therapy. It has rarely been studied systematically, whether homeopathic care is of benefit for cancer patients. METHODS: We conducted a prospective observational study with cancer patients in two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n = 259), and one cohort with conventionally treated cancer patients (CG; n = 380). For a direct comparison, matched pairs with patients of the same tumour entity and comparable prognosis were to be formed. Main outcome parameter: change of quality of life (FACT-G, FACIT-Sp) after 3 months. Secondary outcome parameters: change of quality of life (FACT-G, FACIT-Sp) after a year, as well as impairment by fatigue (MFI) and by anxiety and depression (HADS). RESULTS: HG: FACT-G, or FACIT-Sp, respectively improved statistically significantly in the first three months, from 75.6 (SD 14.6) to 81.1 (SD 16.9), or from 32.1 (SD 8.2) to 34.9 (SD 8.32), respectively. After 12 months, a further increase to 84.1 (SD 15.5) or 35.2 (SD 8.6) was found. Fatigue (MFI) decreased; anxiety and depression (HADS) did not change. CG: FACT-G remained constant in the first three months: 75.3 (SD 17.3) at t0, and 76.6 (SD 16.6) at t1. After 12 months, there was a slight increase to 78.9 (SD 18.1). FACIT-Sp scores improved significantly from t0 (31.0 - SD 8.9) to t1 (32.1 - SD 8.9) and declined again after a year (31.6 - SD 9.4). For fatigue, anxiety, and depression, no relevant changes were found. 120 patients of HG and 206 patients of CG met our criteria for matched-pairs selection. Due to large differences between the two patient populations, however, only 11 matched pairs could be formed. This is not sufficient for a comparative study. CONCLUSION: In our prospective study, we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment. It would take considerably larger samples to find matched pairs suitable for comparison in order to establish a definite causal relation between these effects and homeopathic treatment.

Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study.

OBJECTIVE: The antihormonal therapy of breast cancer patients with the antiestrogen tamoxifen often induces or aggravates menopausal complaints. As estrogen substitution is contraindicated, herbal alternatives, e.g. extracts of black cohosh are often used. DESIGN: A prospective observational study was carried out in 50 breast cancer patients with tamoxifen treatment. All patients had had surgery, most of them had undergone radiation therapy (87%) and approximately 50% had received chemotherapy. Every patient was treated with an isopropanolic extract of black cohosh (1-4 tablets, 2.5 mg) for 6 months. Patients recorded their complaints before therapy and after 1, 3, and 6 months of therapy using the menopause rating scale (MRS II). RESULTS: The reduction of the total MRS II score under black cohosh treatment from 17.6 to 13.6 was statistically significant. Hot flashes, sweating, sleep problems, and anxiety improved, whereas urogenital and musculoskeletal complaints did not change. In all, 22 patients reported adverse events, none of which were linked with the study medication; 90% reported the tolerability of the black cohosh extract as very good or good. CONCLUSIONS: Black cohosh extract seems to be a reasonable treatment approach in tamoxifen treated breast cancer patients with predominantly psychovegetative symptoms.