Acupuncture vs Massage for Pain in Patients Living With Advanced Cancer: The IMPACT Randomized Clinical Trial.

Importance: Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown. Objective: To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer. Design, Setting, and Participants: A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment). Interventions: Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks. Main Outcomes and Measures: The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life. Results: A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage). Conclusions and Relevance: In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04095234.

Integrin ß3 directly inhibits the Gα13-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.

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 ß3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα13-p115RhoGEF interaction. Furthermore, whereas ß3 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 ß3-derived Gα13-binding peptide or Gα13 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 ß3-derived Gα13-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.

Acupuncture improves certain aspects of sleep in hematopoietic stem cell transplantation patients: a secondary analysis of a randomized controlled trial.

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).

Integrating herbal medicine into oncology care delivery: development, implementation, and evaluation of a novel program.

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.

Acupuncture versus massage for pain in patients living with advanced cancer: a protocol for the IMPACT randomised clinical trial.

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.

Effects of Vigorous Versus Restorative Yoga Practice on Objective Cognition Functions in Sedentary Breast and Ovarian Cancer Survivors: A Randomized Controlled Pilot Trial.

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).

Acupuncture in hematologic malignancies and hematopoietic cell transplantation.

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.

Herbal Formula Shenling Baizhu San for Chronic Diarrhea in Adults: A Systematic Review and Meta-analysis.

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.

Education Competencies for Integrative Oncology-Results of a Systematic Review and an International and Interprofessional Consensus Procedure.

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.

Herbal formula MaZiRenWan (Hemp Seed Pill) for constipation: A systematic review with meta-analysis.

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.

Fear of analgesic side effects predicts preference for acupuncture: a cross-sectional study of cancer patients with pain in the USA.

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.

Acupuncture As a Potential Opioid-Sparing Pain Management Intervention for Patients Undergoing Cancer Treatment.

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.

Reduction of Opioid Use by Acupuncture in Patients Undergoing Hematopoietic Stem Cell Transplantation: Secondary Analysis of a Randomized, Sham-Controlled Trial.

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.

A Technology-Assisted, Brief Mind-Body Intervention to Improve the Waiting Room Experience for Chemotherapy Patients: Randomized Quality Improvement Study.

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.

Integrative Medicine Therapies for Pain Management in Cancer Patients.

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.

Practical Application of "About Herbs" Website: Herbs and Dietary Supplement Use in Oncology Settings.

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.

Combination phosphodiesterase type 4 inhibitor and phosphodiesterase type 5 inhibitor treatment reduces non-voiding contraction in a rat model of overactive bladder.

INTRODUCTION: Current 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. METHODS: Fifty-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 (p<0.05). RESULTS: Bladder & 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. CONCLUSION: A PDE4i and PDE5i combination treatment has potential benefit in reducing OAB symptoms, but future research is needed.

Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

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.

Pilot Study of Self-care Breath Training Exercise for Reduction of Chronic Dyspnea.

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.