Search

IntroductionCurrent treatments for overactive bladder (OAB) are often discontinued due to side effects or lack of efficacy. The goal of this study was to determine if combining a phosphodiesterase type 4 inhibitor (PDE4i); with a type 5 inhibitor (PDE5i); would have a beneficial effect on OAB symptoms and if a reduced dose of PDE4i in combination with PDE5i could also provide a beneficial effect in OAB. We hypothesized that PDE5i and PDE4i combination treatment could be utilized to reduce non-voiding contractions and smooth muscle disruption in a rat model of OAB.MethodsFifty-eight age-matched Sprague-Dawley rats underwent PBOO and daily gavage with PDE4i alone (roflumilast; 1mg/kg), PDE5i alone (tadalafil;10mg/kg), high dose combination (PDE4i 1mg/kg, PDE5i 10mg/kg), low dose combination (PDE4i 0.2mg/kg, PDE5i 10mg/kg), or vehicle for 28 days. Fourteen animals underwent sham PBOO with vehicle. Rats underwent conscious and anesthetized cystometry 28 days after PBOO and were euthanized for qualitative bladder histology. One-way ANOVA on ranks with a Dunn's post hoc test was used to indicate statistically significant differences between groups (pResultsBladder & urethral weight was significantly increased after PBOO with vehicle, PDE4i alone, and PDE5i alone, but not with either combination treatment. Frequency of non-voiding contractions during both conscious and anesthetized cystometry increased significantly after PBOO with vehicle, but not after PDE4i or high dose combination treatments compared to sham PBOO. Threshold pressure for voiding was significantly decreased with high dose combination compared to vehicle. PBOO treated with PDE4i alone or high dose combination showed less bladder smooth muscle fibrosis than vehicle, PDE5i alone, or low dose combination treatments.ConclusionA PDE4i and PDE5i combination treatment has potential benefit in reducing OAB symptoms, but future research is needed.

There is increasing evidence for a role of MaxiK potassium channel-activity in regulating the metabolism and intracellular signaling of non-contractile bladder mucosal tissues. At present however no studies have determined the impact of urothelial MaxiK-activity on overall bladder metabolism. To address this we have investigated the effect of bladder lumen instillation of the MaxiK inhibitor, iberiotoxin (IBTX), on mucosal and detrusor metabolism using metabolomics. Since IBTX does not cross plasma membranes, when instilled into the bladder lumen it would only effect urothelially expressed MaxiK-activity. Surprisingly IBTX treatment caused more effect on the metabolome of the detrusor than mucosa (the levels of 17% of detected detrusor metabolites were changed in comparison to 6% of metabolites in mucosal tissue following IBTX treatment). In mucosal tissues, the major effects can be linked to mitochondrial-associated metabolism whereas in detrusor there were additional changes in energy generating pathways (such as glycolysis and the TCA cycle). In the detrusor, changes in metabolism are potentially a result of IBTX effecting MaxiK-linked signaling pathways between the mucosa and detrusor, secondary to changes in physiological activity or a combination of both. Overall we demonstrate that urothelial MaxiK-activity plays a significant role in determining mitochondrially-associated metabolism in mucosal tissues, which effects the metabolism of detrusor tissue. Our work adds further evidence that the urothelium plays a major role in determining overall bladder physiology. Since decreased MaxiK-activity is associated with several bladder pathophysiology's, the changes in mucosal metabolism reported here may represent novel downstream targets for therapeutic interventions.

The urokinase plasminogen activator receptor (uPAR) regulates macrophage adhesion and migration by binding directly to matrix proteins and signaling through integrin complexes. In this study, we examined the role of uPAR on macrophage infiltration into the vascular wall. Stable murine macrophage (Raw264.7) cell lines expressing high levels of human uPAR, human urokinase plasminogen activator (uPA), or both were established using expression vectors driven by the human CD68 promoter. Stimulation with human uPA specifically induced phosphorylation of early response regulated kinase (ERK) in cells expressing human uPAR but not in sham transfected cells. The human uPAR expressing Raw264.7 cells showed increased adhesion to both human uPA and vitronectin (Vn). Raw264.7 cells expressing human uPAR or both human uPAR and uPA, but not uPA alone, were detected in the aortic wall of ApoE-/- mice, and no cells were detected in that of age-matched C57BL/6J mice after intravenous infusion of the cells. Blocking of Mac-1/ICAM-1 interaction by anti-aM antibody (M1/70) significantly reduced the infiltration of huPAR-expressing Raw264.1 cells into aorta of ApoE-/- mice. Treatment of C57BL/6J mice with angiotensin II resulted in infiltration of Raw264.7 cells expressing human uPAR. These data demonstrate that uPAR plays a key role in promoting macrophage infiltration into the arterial wall of ApoE-/- mice. 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) is associated with a high symptom burden including sleep disturbance. Here we present the results of a secondary analysis of a randomized, sham-controlled trial assessing the effect of acupuncture on sleep quality during HSCT., Methods: Adult multiple myeloma patients undergoing inpatient and outpatient autologous HSCT were randomized and blinded to receive either true or sham acupuncture (by licensed acupuncturists) once daily for 5 days starting the day after chemotherapy. Sleep onset, total sleep time, sleep efficiency percentage and sleep-onset latency time were assessed using an actigraphy-based sleep monitor. A multivariate regression analysis was conducted to compare the average area-under-the-curve of five acupuncture intervention days for each sleep outcome between groups, adjusted by baseline score and inpatient or outpatient chemotherapy stratum., Results: Over 32 months, 63 patients were enrolled. Participants undergoing true acupuncture experienced a significant improvement in sleep efficiency when compared to sham (-6.70, 95% CI -13.15, -0.25, p = 0.042). Subgroup analysis showed that the improvement was more prominent in the inpatient setting (-9.62, 95% CI -18.76, -0.47; p = 0.040). True acupuncture tended to improve wake time after sleep onset (WASO; -10.95, p = 0.054). Between-group differences in other sleep related variables were not statistically significant., Conclusion: Our data suggest that true acupuncture may improve certain aspects of sleep, including sleep efficiency and possibly WASO, in multiple myeloma patients undergoing HSCT. By studying patient reported outcomes in future larger scale studies, acupuncture's role in improving sleep quality during HSCT treatment could be further elucidated., Trial Registration Number: NCT01811862 (ClinicalTrials.gov)., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Dr SG has received research funding from Amgen, Janssen, Celgene, Quintiles, Pfizer, CSL Behring, Sanofi, Adienne, Kite, JAZZ and Actinuum. The remaining authors declare no competing financial interests.

The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that β 3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα 13 -p115RhoGEF interaction. Furthermore, whereas β 3 deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a β 3 -derived Gα 13 -binding peptide or Gα 13 knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the β 3 -derived Gα 13 -binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion., (© 2023. Springer Nature Limited.)

Objective: To evaluate the feasibility of a novel program facilitating patient-provider communication about appropriate use of herbal medicine at a large academic cancer center and its impact on patient wellbeing., Methods: In the Herbal Oncology Program (HOP), integrative medicine providers counseled patients about unmet symptom needs and prescribed traditional Chinese medicine (TCM) herbs when indicated, taking into consideration the clinical context, patient preference, and research evidence. To evaluate the feasibility and outcomes, we performed a retrospective analysis using medical record data (symptoms and other concerns that motivated patients to seek herbal products, types and numbers of dispensed TCM herbs, and demographic characteristics). We also conducted a survey to assess patient experience and satisfaction., Results: All 851 participants were outpatients, with 712 (84%) in active treatment. HOP dispensed 1266 herbal prescriptions for a range of symptoms, most commonly GI symptoms (467, 37%); pain (353, 28%); and treatment-related fatigue, sleep, and mood disorders (346, 27%). Of 269 patients invited to the survey, 107 (40%) completed it. A majority of respondents 70.9% (73/103) were satisfied with the effectiveness of dispensed herbs in relieving their symptoms, and few 6.7% (7/104) had experienced mild adverse events that resolved after discontinuing herbal use., Conclusions: The study's findings support the feasibility of integrating herbal medicine into an academic oncology setting. Patient satisfaction with HOP was high, with limited adverse events. The patterns of herbal prescriptions in HOP suggest future areas for clinical research to strengthen the evidence base around safe and effective use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acupuncture is an integrative medicine modality that has been used historically and studied recently for managing various symptoms and diseases. Patients with hematological malignancies often experience a high symptom burden including pain, fatigue, nausea, vomiting, and insomnia. Pharmacological interventions are the mainstay of managing these symptoms, although they may not provide adequate control or are not well tolerated due to side effects. There have been many randomized controlled trials of acupuncture on reduction of these symptoms. In this review, we will summarize the current evidence on the effect of acupuncture on the management of common symptoms experienced by patients with hematological malignancies and the current understanding of acupuncture's mechanism of action. The evidence is the strongest for reducing pain and nausea vomiting, less strong for symptoms such as peripheral neuropathy, fatigue, constipation, insomnia, night sweat, and pruritus., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Pain, comorbid fatigue and sleep disturbances are common and distressing symptoms for patients with advanced cancer, negatively impacting their quality of life. Clinical guidelines recommend non-pharmacological interventions, including acupuncture and massage, for pain management in adult patients with cancer in adjunct to conventional care. However, high-quality evidence about the comparative effectiveness and long-term durability of these therapies for symptom management is limited., Methods and Analysis: We describe the design of a two-arm, parallel group, multicentre randomised controlled trial that investigates the use of acupuncture versus massage for musculoskeletal pain among 300 patients with diverse types of advanced cancer. The primary aim is to evaluate the long-term effectiveness (26 weeks from randomisation) of acupuncture vs massage for pain (primary outcome) and comorbid symptoms (fatigue, sleep disturbance and quality of life). The secondary aim is to identify patient-level demographic characteristics (eg, sex, race, age), clinical factors (eg, insomnia, pain severity) and psychological attributes that are associated with a greater reduction in pain for either acupuncture or massage. Patients will receive weekly acupuncture or massage treatments for 10 weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint will be the change in worst pain intensity score from baseline to 26 weeks. We will collect validated patient-reported outcomes at multiple time points over 26 weeks., Ethics and Dissemination: The Institutional Review Board at Memorial Sloan Kettering Cancer Center in New York approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Our findings will help patients and healthcare providers make informed decisions about incorporating non-pharmacological treatments to manage pain for patients with advanced cancer., Trial Registration Number: NCT04095234., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Integrative oncology is a burgeoning field and typically provided by a multiprofessional team. To ensure cancer patients receive effective, appropriate, and safe care, health professionals providing integrative cancer care should have a certain set of competencies. The aim of this project was to define core competencies for different health professions involved in integrative oncology. The project consisted of two phases. A systematic literature review on published competencies was performed, and the results informed an international and interprofessional consensus procedure. The second phase consisted of three rounds of consensus procedure and included 28 experts representing 7 different professions (medical doctors, psychologists, nurses, naturopathic doctors, traditional Chinese medicine practitioners, yoga practitioners, patient navigators) as well as patient advocates, public health experts, and members of the Society for Integrative Oncology. A total of 40 integrative medicine competencies were identified in the literature review. These were further complemented by 18 core oncology competencies. The final round of the consensus procedure yielded 37 core competencies in the following categories: knowledge (n = 11), skills (n = 17), and abilities (n = 9). There was an agreement that these competencies are relevant for all participating professions. The integrative oncology core competencies combine both fundamental oncology knowledge and integrative medicine competencies that are necessary to provide effective and safe integrative oncology care for cancer patients. They can be used as a starting point for developing profession-specific learning objectives and to establish integrative oncology education and training programs to meet the needs of cancer patients and health professionals., (© 2020. The Author(s).)

Purpose: Many cancer survivors experience cancer-related cognitive impairment (CRCI). We conducted a randomized controlled pilot trial of 2 types of yoga practice and evaluated their effects on participants' objective cognitive function., Methods: Sedentary breast or ovarian cancer survivors were randomized to practice either restorative yoga (with more meditative practice and minimal physical exertion) or vigorous yoga (with considerable physical exertion and minimal meditative practice) in 60-minute supervised sessions 3 times a week for 12 weeks, followed by 12 weeks of home practice. We used the NIH Toolbox Cognition Domain to evaluate participants at baseline, week 12, and week 24., Results: We enrolled 35 participants. For women in the restorative yoga group, overall cognitive function was statistically significantly improved at weeks 12 and 24 compared to baseline ( P  = .03 and 0.004; Cohen's D  = 0.3 and 0.5). Fluid cognitive function also significantly improved at weeks 12 and 24 ( P  = .02 and 0.0007; Cohen's D  = 0.3 and 0.6), whereas improvements in crystallized cognition were not significant. For women in the vigorous yoga group, significant improvement was only seen in tasks of crystallized cognition at week 24 ( P  = .03; Cohen's D  = 0.5). Between-group comparisons showed that at week 24, women in the restorative yoga group had significantly higher scores on fluid cognition tasks., Conclusions: Patients who participated in yoga practice demonstrated improvement in objective cognitive function over time. Restorative yoga may be more effective in improving fluid cognitive function at week 24 when compared to vigorous yoga. These promising findings should be confirmed in definitive studies., Trial Registration: Clinicaltrials.gov; NCT02305498 (Date Registered: December 2, 2014).

Background: Shenling Baizhu San (SBS), a well-known Chinese medicine herbal formula, has been widely used for treating chronic diarrhea for thousands of years. However, the efficacy and safety of SBS in treating chronic diarrhea have not been fully assessed., Objective: This study evaluates the efficacy and safety of the herbal formula SBS in symptomatic relief of chronic diarrhea., Methods: English and Chinese language databases (PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and SinoMed electronic databases) were searched through April 2020 for relevant randomized controlled trials (RCTs). The outcomes in these RCTs included stool frequency, stool consistency, patient-reported satisfaction of chronic diarrhea treatment, quality of life and adverse events. Paired reviewers independently extracted data and conducted qualitative and quantitative analyses. The Cochrane revised risk of bias RoB-2 tool was applied to assess the risk of bias for each trial whereas the RevMan 5.3 software was used for outcomes data synthesis and meta-analysis. Mean difference (MD) and the 95% confidence interval (CI) were used to measure continuous data. The dichotomous data were analyzed via the relative risk (RR) with 95% CIs., Results: Fourteen RCTs including 1158 participants (54% males) with chronic diarrhea were included. Shenling Baizhu San combined with or without conventional medicine (CM) was associated with greater patient-reported satisfaction than CM alone. There was no increased risk of adverse events (AEs) during treatment., Conclusion: Treatment with SBS was associated with significant improvement in patient-reported satisfaction, irrespective of conventional medicine use. Rigorous and powered RCTs with objective outcome measures are needed to confirm the effects of SBS in specific gastrointestinal disease populations with chronic diarrhea symptoms., Systematic Review Registration Number (prospero): CRD42020178073.

Background: There is growing interest in using herbal supplements to treat constipation; however, little evidence exists for their use., Purpose: This study evaluates the efficacy and safety of herbal formula MaZiRenWan (Hemp Seed Pill, HSP) in patients with functional or non-functional constipation., Study Design: Systematic review and meta-analysis METHODS: PubMed, CENTRAL, Embase, CNKI, and Wanfang were searched through April 20, 2020 for randomized trials of HSP versus placebo or medications for all types of constipation. The primary outcomes were complete response rate, complete spontaneous bowel movement (CSBM), patient-reported satisfactory treatment rate (prSTR), and adverse events (AEs). Clinical data were analyzed using a random-effects model, and the quality of evidence was evaluated with the GRADE system., Results: This review includes 1681 constipation patients from 17 moderate-to-high risk of bias trials that were conducted in east Asia. Two high-quality trials showed that HSP compared with placebo significantly increased weekly CSBM (mean difference, 0.95; 95% CI: 0.56, 1.35) and had a higher complete response rate (risk ratio [RR], 1.43; 95% CI: 1.20, 1.71) in patients with functional constipation. Low-quality evidence showed significant improvement in prSTR in HSP compared with conventional medications (RR, 1.79; 95% CI: 1.42, 2.25). Additionally, HSP use did not increase AEs compared with no HSP (p = 0.99)., Conclusions: This study found that HSP was effective among Asian patients with functional constipation. Rigorous trials need to be conducted in clinical populations outside of east Asia and in those with non-functional constipation to increase the generalizability of the evidence., (Copyright © 2021. Published by Elsevier GmbH.)

Purpose: Approximately one in two cancer patients globally are under-treated for pain. Opioids and other analgesics represent the mainstay of cancer pain management; however, barriers to their use are well-documented. We evaluated whether acupuncture would be a preferable treatment option among cancer patients with attitudinal barriers to pharmacological pain management., Methods: We conducted a cross-sectional survey of cancer patients at a tertiary urban cancer center and eleven suburban/rural hospitals in the Northeastern United States. We assessed attitudinal barriers to pharmacological pain management with the Barriers Questionnaire (BQ-13). The BQ-13 consists of two subscales: pain management beliefs and analgesic side effects. We also asked patients whether they prefer acupuncture, analgesics, or have no preference between these two modalities for pain management. Covariates included sociodemographics, clinical characteristics, and attitudes/beliefs about acupuncture. We used logistic regression to examine the association between attitudinal barriers and acupuncture preference., Results: Among 628 patients, 197 (31.4%) preferred acupuncture for pain management, 146 (23.3%) preferred analgesics, and 285 (45.4%) had no preference. The highest reported attitudinal barriers were fear of addiction and fear of analgesic-associated constipation and nausea. Adjusting for covariates, we found that attitudinal barriers related to fear of analgesic side effects were significantly associated with acupuncture preference (adjusted odds ratio [AOR] 1.45, 95% confidence interval [CI] 1.17-1.81), but barriers related to pain management beliefs were not (AOR 1.17, 95% CI 0.91-1.51). Attitudes/beliefs about acupuncture (i.e., greater expected benefits, fewer perceived barriers, and more positive social norms) and female gender also predicted acupuncture preference, whereas race and educational status did not., Conclusion: Acupuncture may be a preferable treatment option among cancer patients at risk of inadequately controlled pain due to fear of analgesic side effects. Evidence-based integration of acupuncture and analgesics, guided by patient treatment preferences, represents an essential aspect of patient-centered care and has potential to address unmet cancer pain management needs.

Background: High-symptom burdens, including pain, are associated with high-dose chemotherapy. Objective: We conducted a pilot study to evaluate how acupuncture may affect symptom burden and use of pain medication. Design: This is a randomized sham acupuncture (SA) controlled trial. Setting: An academic cancer center. Patients: Patients were with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Intervention: Once daily acupuncture for 5 days after high-dose chemotherapy. Main Outcome Measures: M. D. Anderson Symptom Inventory (MDASI), opioid use. Results: Compared with SA, true acupuncture reduced nausea, poor appetite, and drowsiness, and use of opioids in opioid-naive patients. Randomizations: Yes. Blinding: Investigators and study participants were blinded. Conclusion: Further study of acupuncture in a larger trial is warranted for its effect on reducing opioid use and symptom burdens during high-dose chemotherapy. Registration: NCT01811862., Competing Interests: No competing financial interests exist., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)

Objective: To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT)., Methods: Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation., Results: Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P = 0.86)., Conclusions: Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients waiting for chemotherapy can experience stress, anxiety, nausea, and pain. Acupressure and meditation have been shown to control such symptoms., Objective: This study aimed to evaluate the feasibility and effectiveness of an integrative medicine app to educate patients about these self-care tools in chemotherapy waiting rooms., Methods: We screened and enrolled cancer patients in chemotherapy waiting rooms at two Memorial Sloan Kettering Cancer Center locations. Patients were randomly assigned into an intervention arm in which subjects watched acupressure and meditation instructional videos or a control arm in which they watched a time- and attention-matched integrative oncology lecture video. Before and after watching the videos, we asked the patients to rate four key symptoms: stress, anxiety, nausea, and pain. We performed the analysis of covariance to detect differences between the two arms postintervention while controlling for baseline symptoms., Results: A total of 223 patients were enrolled in the study: 113 patients were enrolled in the intervention arm and 110 patients were enrolled in the control arm. In both groups, patients showed significant reductions in stress and anxiety from baseline (all P<.05), with the treatment arm reporting greater stress and anxiety reduction than the control arm (1.64 vs 1.15 in stress reduction; P=.01 and 1.39 vs 0.78 in anxiety reduction; P=.002). The majority of patients reported that the videos helped them pass time and that they would watch the videos again., Conclusions: An integrative medicine self-care app in the waiting room improved patients' experiences and reduced anxiety and stress. Future research could focus on expanding this platform to other settings to improve patients' overall treatment experiences., (©Ting Bao, Gary Deng, Lauren A DeMarzo, W Iris Zhi, Janice L DeRito, Victoria Blinder, Connie Chen, Qing S Li, Jamie Green, Eva Pendleton, Jun J Mao. Originally published in JMIR Cancer (http://cancer.jmir.org), 07.11.2019.)

The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains About Herbs (www.aboutherbs.com), which provides summaries of research data including purported uses, adverse effects, and herb-drug interactions for about 284 dietary supplements. Using Google Analytics, we found the website registered more than 26,317,000 hits since November 2002. The 10 most searched-for herbs/supplements of 2018 are chaga mushroom, turmeric, ashwagandha, reishi mushroom, graviola, Active Hexose-Correlated Compound, boswellia, dandelion, green tea, and Coriolus versicolor. Here we discuss their safety, herb-drug interactions, and appropriate uses in the oncology setting, based on literature searches in PubMed. Over the past 16 years, the evidence for use of these supplements is based mostly on preclinical findings, with few well-designed studies and limited trials conducted in cancer patients. It is important to familiarize health care professionals about popular supplements, so patients can be informed to make decisions that maximize benefits and minimize risks.

Pain management for cancer patients should include pharmacologic and nonpharmacologic interventions. Integrative medicine therapies, such as mind-body practice, acupuncture, massage therapy, and music therapy, have been studied for their roles in pain management. Data from randomized controlled trials support the effect of hypnosis, acupuncture, and music therapy in reduction of pain. Mindfulness meditation, yoga, qigong, and massage therapy, although may not reduce pain per se, can relieve anxiety and mood changes, which are commonly associated with pain. In clinical practice, one should also consider burdens and risks to patients, patient preference, and the presence or absence of better alternatives when making decisions on whether an integrative medicine therapy is of clinical value.

Objective: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice., Study Design: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals. In the first study, we enrolled children in the ED requiring intravenous cannulation or venipuncture. In the second, we enrolled children in outpatient pathology requiring venipuncture. In the ED, 64 children were assigned to virtual reality and 59 to SOC. In pathology, 63 children were assigned to virtual reality and 68 to SOC; 2 children withdrew assent in the SOC arm, leaving 66. The primary endpoint was change from baseline pain between virtual reality and SOC on child-rated Faces Pain Scale-Revised., Results: In the ED, there was no change in pain from baseline with SOC, whereas virtual reality produced a significant reduction in pain (between-group difference, -1.78; 95% CI, -3.24 to -0.317; P = .018). In pathology, both groups experienced an increase in pain from baseline, but this was significantly less in the virtual reality group (between-group difference, -1.39; 95% CI, -2.68 to -0.11; P = .034). Across both studies, 10 participants experienced minor adverse events, equally distributed between virtual reality/SOC; none required pharmacotherapy., Conclusions: In children aged 4-11 years of age undergoing intravenous cannulation or venipuncture, virtual reality was efficacious in decreasing pain and was safe., Trial Registration: Australia and New Zealand Clinical Trial Registry: ACTRN12617000285358p., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With the increase in utilization of alternative medications to manage cancer treatment-related side effects, pharmacovigilance of alternative drug therapies, specifically herbal supplements, has become of increasing importance in the oncologic setting. This chapter focuses on the pharmacovigilance of herbal supplements in the setting of cancer drug therapy and explores national and international drug policies that have been employed to mitigate adverse herbal supplement events (AHEs). This chapter examines common drug-herbal supplement interactions, discusses the mechanisms behind these interactions, and investigates several common pharmacovigilance reporting methods clinicians can use to report adverse events. This chapter will also describe policies and strategies that can be employed to monitor use of these alternative drug therapies, and examines global harmonization efforts to reduce AHEs in the cancer setting. The safety of herbal medicines has emerged as an international public health priority, and we explore how oncology providers may directly apply the knowledge garnered herein to help guide their clinical management of oncology patients utilizing alternative medications.

Purpose: Dyspnea related to chronic pulmonary disorders is difficult to manage. In this single-arm study, we evaluated feasibility and potential efficacy of a self-care breath training program to reduce dyspnea that persists despite standard treatments in patients with chronic lung disease., Methods: Adult patients with a chronic pulmonary disorder and stable moderate dyspnea received one 30-min training on specific breathing techniques, followed by audio-guided at-home practice 15 min twice daily for 6 wk, supported with weekly telephone monitoring/coaching. The feasibility endpoints, Baseline and Transition Dyspnea Indexes, 6-min walk test, Hospital Anxiety and Depression Scale, and oxygen saturation at rest and exercise were evaluated at baseline and wk 6., Results: Of the 23 patients enrolled over 2 yr, 19 completed the study. A majority (74%; 95% CI, 49%-91%) completed at least 75% of the home practice sessions. Significant objective improvements in physical performance, defined as distance walked, were observed after 6 wk of intervention. On average, patients walked significantly further in the 6-min walk test (59 ft; 95% CI, 18-99; P = .007). In addition, 53% reported clinically significant (20%, defined a priori) subjective improvement in the Transition Dyspnea Index, although the difference was not statistically significant (0.7; 95% CI, -0.8 to 2.3; P = .3). No significant differences were seen in the Hospital Anxiety and Depression Scale or oxygen saturation., Conclusions: A low-burden, low-cost, self-care breath training program improved distance walked by patients with chronic dyspnea after 6 wk of home practice. Promising data suggest that a randomized trial of this breath training program is warranted.

Yoga has been shown to improve cancer survivors' quality of life, yet regular yoga practice is a challenge for those who are sedentary. We conducted a pilot randomized controlled study to assess feasibility and adherence of two types of yoga intervention among sedentary cancer survivors. Sedentary breast and ovarian cancer survivors were randomized to practice either restorative yoga (minimal physical exertion, Group R) or vigorous yoga (considerable physical exertion, Group V) in three 60-minute supervised sessions a week for 12 weeks, followed by 12 weeks of home practice. Accrual, adherence, and attendance rates were assessed. Of the 226 eligible patients, 175 (77%) declined to participate in the study, citing time commitment and travel as the most common barriers. Forty-two subjects consented to participate in the study. Of the 35 participants who began the intervention (20 in Group R and 15 in Group V), adherence rate (percentage remaining in the study at week 12) was 100% and 87%, respectively. Rate of adequate attendance (more than 66% of the scheduled supervised sessions) was 85% and 73%, respectively. Rate of completion of the home practice period was 85% and 77%, respectively. In this study, sedentary cancer survivors were able to adhere to a long-term, regular yoga regimen. The rate of adequate attendance was higher for restorative yoga. Future studies for sedentary patients should focus on reducing time commitment and travel requirements to improve recruitment, and on using restorative yoga as a more feasible intervention for this population.

This article summarizes the current evidence regarding the use of acupuncture for pain management in cancer patients. It includes a description of how acupuncture is thought to work and what the intervention entails, data on acupuncture for managing pain caused by cancer or by cancer treatment (radiation, chemotherapy, endocrine therapy), how acupuncture is practiced in the US medical system, discussion of safety issues, and practical tips on how to integrate acupuncture into cancer care.

Purpose: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT., Methods: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation., Results: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017)., Conclusions: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study., Trial Registration: NCT01811862.

Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Suicidal patients often visit healthcare professionals in their last month before suicide, but medical practitioners are unlikely to raise the issue of suicide with patients because of time constraints and uncertainty regarding an appropriate approach., Introduction: A brief tool called the e-PASS Suicidal Ideation Detector (eSID) was developed for medical practitioners to help detect the presence of suicidal ideation (SI) in their clients. If SI is detected, the system alerts medical practitioners to address this issue with a client. The eSID tool was developed due to the absence of an easy-to-use, evidence-based SI detection tool for general practice., Material and Methods: The tool was developed using binary logistic regression analyses of data provided by clients accessing an online psychological assessment function. Ten primary healthcare professionals provided advice regarding the use of the tool., Results: The analysis identified eleven factors in addition to the Kessler-6 for inclusion in the model used to predict the probability of recent SI. The model performed well across gender and age groups 18-64 (AUR 0.834, 95% CI 0.828-0.841, N = 16,703). Healthcare professionals were interviewed; they recommended that the tool be incorporated into existing medical software systems and that additional resources be supplied, tailored to the level of risk identified., Conclusion: The eSID is expected to trigger risk assessments by healthcare professionals when this is necessary. Initial reactions of healthcare professionals to the tool were favorable, but further testing and in situ development are required.

Traditional oriental herbal medicine (HM) is used by cancer patients to improve immunity. Natural killer (NK) cells are associated with development and progression of tumor and survival of cancer patients. This literature review examined randomized controlled trials (RCTs) in four electronic databases until October 2015 to evaluate the effects of oral HM on NK cells in cancer patients. Data were pooled and computed in a meta-analysis. The methodological quality was assessed according to the Cochrane risk of bias tool. Sixteen RCTs involving 1326 cancer patients were identified. Combination of HM and conventional treatment was associated with significantly higher level of NK cells compared with conventional cancer treatments (standardized mean difference, 1.218; 95% confidence interval 0.719-1.717; p < 0.001). Eight RCTs reported statistically significant improvements in the proportions or activity of NK cells in patient groups who received both HM and conventional treatment compared with patients who received conventional treatment alone, while eight RCTs reported no statistically significant differences between the two groups. Studies (n = 16) included in this review had insufficient quality of evidence with unclear (n = 1) and high (n = 15) values of the risk of bias. Although traditional oriental HM may have the positive effects on preserving the level of NK cells in cancer patients receiving conventional treatments, current evidence is inconclusive because of lack of high-quality evidence. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR., (©2016 American Association for Cancer Research.)

Context and Objectives: The unmonitored use of herbal medicinal remedies by patients with cancer presents a significant challenge to oncology healthcare professionals. We describe an increasingly popular herbal "wonder drug," Ephedra foeminea (Alanda in Arabic), whose use has spread from the Palestinian patient population throughout the Middle East. We conducted a multicentered and multidisciplinary collaborative research effort in order to understand the potential benefits and harms of this popular herbal remedy., Methods: We conducted an in-depth search of the medical literature, both traditional and modern, for any mention of the clinical use of Alanda for the treatment of cancer. We then tested the remedy, first for toxic ephedra alkaloid components and then for anticancer effects, as well as effects on the cytotoxic activity of chemotherapy agents (cisplatin and carboplatin) on breast cancer cell cultures., Results: We found no mention in the literature, both conventional and traditional, on the use of Alanda for the treatment of cancer. Laboratory testing did not find any toxic components (i.e., ephedra alkaloids) in the preparation. However, in vitro exposure to Alanda led to a reduced cytotoxic effect of chemotherapy on breast cancer cell cultures., Conclusions: The use of an integrative ethnobotanical, laboratory and clinical research-based approach can be extremely helpful when providing nonjudgmental and evidence-based guidance to patients with cancer, especially on the use of traditional herbal medicine. The effectiveness and safety of these products need to be examined by integrative physicians who are dually trained in both complementary medicine and supportive cancer care.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-L-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. L-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-L-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: An increasing number of clinics offer complementary or integrative medicine services; however, clear guidance about how complementary medicine could be successfully and efficiently integrated into conventional health care settings is still lacking. Combining conventional and complementary medicine into integrative medicine can be regarded as a kind of merger. In a merger, two or more organizations - usually companies - are combined into one in order to strengthen the companies financially and strategically. The corporate culture of both merger partners has an important influence on the integration., Purpose: The aim of this project was to transfer the concept of corporate culture in mergers to the merging of two medical systems., Methods: A two-step approach (literature analyses and expert consensus procedure) was used to develop practical guidance for the development of a cultural basis for integrative medicine, based on the framework of corporate culture in "mergers," which could be used to build an integrative medicine department or integrative medicine service., Results: Results include recommendations for general strategic dimensions (definition of the medical model, motivation for integration, clarification of the available resources, development of the integration team, and development of a communication strategy), and recommendations to overcome cultural differences (the clinic environment, the professional language, the professional image, and the implementation of evidence-based medicine)., Conclusion: The framework of mergers in corporate culture provides an understanding of the difficulties involved in integrative medicine projects. The specific recommendations provide a good basis for more efficient implementation.

Background: The majority of breast cancer patients use complementary and/or integrative therapies during and beyond cancer treatment to manage symptoms, prevent toxicities, and improve quality of life. Practice guidelines are needed to inform clinicians and patients about safe and effective therapies., Methods: Following the Institute of Medicine's guideline development process, a systematic review identified randomized controlled trials testing the use of integrative therapies for supportive care in patients receiving breast cancer treatment. Trials were included if the majority of participants had breast cancer and/or breast cancer patient results were reported separately, and outcomes were clinically relevant. Recommendations were organized by outcome and graded based upon a modified version of the US Preventive Services Task Force grading system., Results: The search (January 1, 1990-December 31, 2013) identified 4900 articles, of which 203 were eligible for analysis. Meditation, yoga, and relaxation with imagery are recommended for routine use for common conditions, including anxiety and mood disorders (Grade A). Stress management, yoga, massage, music therapy, energy conservation, and meditation are recommended for stress reduction, anxiety, depression, fatigue, and quality of life (Grade B). Many interventions (n = 32) had weaker evidence of benefit (Grade C). Some interventions (n = 7) were deemed unlikely to provide any benefit (Grade D). Notably, only one intervention, acetyl-l-carnitine for the prevention of taxane-induced neuropathy, was identified as likely harmful (Grade H) as it was found to increase neuropathy. The majority of intervention/modality combinations (n = 138) did not have sufficient evidence to form specific recommendations (Grade I)., Conclusions: Specific integrative therapies can be recommended as evidence-based supportive care options during breast cancer treatment. Most integrative therapies require further investigation via well-designed controlled trials with meaningful outcomes., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Integrative oncology, the diagnosis-specific field of integrative medicine, addresses symptom control with nonpharmacologic therapies. Known commonly as "complementary therapies" these are evidence-based adjuncts to mainstream care that effectively control physical and emotional symptoms, enhance physical and emotional strength, and provide patients with skills enabling them to help themselves throughout and following mainstream cancer treatment. Integrative or complementary therapies are rational and noninvasive. They have been subjected to study to determine their value, to document the problems they ameliorate, and to define the circumstances under which such therapies are beneficial. Conversely, "alternative" therapies typically are promoted literally as such; as actual antitumor treatments. They lack biologic plausibility and scientific evidence of safety and efficacy. Many are outright fraudulent. Conflating these two very different categories by use of the convenient acronym "CAM," for "complementary and alternative therapies," confuses the issue and does a substantial disservice to patients and medical professionals. Complementary and integrative modalities have demonstrated safety value and benefits. If the same were true for "alternatives," they would not be "alternatives." Rather, they would become part of mainstream cancer care. This manuscript explores the medical and sociocultural context of interest in integrative oncology as well as in "alternative" therapies, reviews commonly-asked patient questions, summarizes research results in both categories, and offers recommendations to help guide patients and family members through what is often a difficult maze. Combining complementary therapies with mainstream oncology care to address patients' physical, psychologic and spiritual needs constitutes the practice of integrative oncology. By recommending nonpharmacologic modalities that reduce symptom burden and improve quality of life, physicians also enable patients to play a role in their care. Critical for most patients, this also improves the physician-patient relationship, the quality of cancer care, and the well-being of patients and their families.

Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient's perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today's informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks.

Purpose: Many cancer patients experience persistent fatigue after the completion of chemotherapy. A previous single-arm study provided evidence for an effect of acupuncture in this population. We conducted a randomized controlled trial to determine whether acupuncture reduces post-chemotherapy chronic fatigue more effectively than sham acupuncture., Methods: Cancer patients reporting significant fatigue persisting for at least 2 months following the completion of chemotherapy were randomized to receive once weekly true or sham acupuncture for 6 weeks. Fatigue was evaluated before and after treatment using the Brief Fatigue Inventory (BFI, the primary endpoint). Secondary endpoints included the Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Cancer Treatment-General (FACT-G) scores., Results: One hundred one patients were randomized with 74 (34 true acupuncture; 40 sham control) evaluated for the primary endpoint. BFI scores fell by about one point between baseline and follow-up in both groups with no statistically significant difference between groups. HADS and FACT-G scores also improved in both groups, but there was no significant difference between groups. Patients in the sham acupuncture group crossed over to receive true acupuncture in week 7. No long-term reduction of fatigue scores was observed at the 6-month evaluation., Conclusions: True acupuncture as provided in this study did not reduce post-chemotherapy chronic fatigue more than did sham acupuncture. The study is limited by the number of patients lost to follow-up. We also cannot exclude the possibility that a more intensive treatment regimen may be more effective.

Purpose: Postoperative ileus (POI) prolongs hospital stay and increases risk of postoperative complications. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture reduces POI more effectively than sham acupuncture., Methods: Colon cancer patients undergoing elective colectomy were randomized to receive 30 min of true or sham acupuncture twice daily during their first 3 postoperative days. GI-3 (the later of the following two events: time that the patient first tolerated solid food, AND time that the patient first passed flatus OR a bowel movement) and GI-2 (the later of the following two events: time patient first tolerated solid food AND time patient first passed a bowel movement) were determined. Pain, nausea, vomiting, and use of pain medications were evaluated daily for the first 3 postoperative days., Results: Ninety patients were randomized. Eighty-one received the allocated intervention: 39 in the true acupuncture group and 42 in the sham acupuncture group, all evaluated for the primary endpoint. The mean time to GI-3 was 149 h [standard deviation (SD) 71 h] and 146 (SD 62 h) after surgery for the acupuncture group and the sham acupuncture group (difference between means -2 h; 95 % confidence interval -31, 26; p = 0.9). No significant differences were found between groups for secondary endpoints., Conclusions: True acupuncture as provided in this study did not reduce POI more significantly than sham acupuncture. The study was limited by a standard deviation much larger than expected, suggesting that a study with a larger sample size might be required.