Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial.

BACKGROUND: Chronic pain negatively affects sleep; it is unclear whether pain relief from acupuncture contributes to sleep quality improvements in cancer survivors. This study aimed to evaluate the effect of acupuncture versus usual care on sleep quality among cancer survivors with comorbid sleep disturbance and chronic musculoskeletal pain. METHODS: Sleep outcome data from the Personalized Electroacupuncture Versus Auricular Acupuncture Comparative Effectiveness (PEACE) randomized clinical trial were analyzed. Electroacupuncture or auricular acupuncture was compared with usual care for sleep quality improvement over 10 weeks of treatment among cancer survivors with clinically significant sleep disturbance and chronic musculoskeletal pain at baseline. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) global score. RESULTS: Among 268 participants (mean [standard deviation (SD)] age, 61.4 [12.6] years; 191 women [71.3%]; mean [SD] baseline PSQI global score, 10.3 [3.3] points), electroacupuncture and auricular acupuncture resulted in greater reductions in the PSQI global score from baseline to 10 weeks in comparison with usual care: 1.42 points (95% confidence interval [CI], 0.45-2.38; p = .004) and 1.59 points (95% CI, 0.62-2.55; p = .001), respectively. The improvement in sleep quality for the acupuncture groups was sustained for 24 weeks from randomization. Furthermore, a greater proportion of patients in the electroacupuncture and auricular acupuncture groups had clinically meaningful improvement in sleep quality compared to the usual care group (41.0% and 42.9% vs. 21.4%; p = .044). CONCLUSIONS: Among cancer survivors with comorbid sleep disturbance and chronic pain, electroacupuncture and auricular acupuncture produced a clinically relevant and persistent improvement in sleep quality. These findings suggest that acupuncture may be an evidence-based nonpharmacologic intervention to improve sleep health for cancer survivors with pain. PLAIN LANGUAGE SUMMARY: This study analyzed the sleep quality data from a published randomized clinical trial that evaluated the effect of electroacupuncture or auricular acupuncture versus usual care on pain relief among people who survived cancer. This analysis included a prespecified subgroup of 268 participants with co-occurring sleep disturbance and chronic musculoskeletal pain at baseline and found that patients who used acupuncture for pain relief demonstrated greater improvements in sleep quality compared with patients who received usual care. Sleep quality improvement by acupuncture was sustained after the treatment ended.

The relationship between anxiety and vaginal-related sexual health in postmenopausal breast cancer survivors on aromatase inhibitors therapies: a cross sectional study.

PURPOSE: Sexual health problems and anxiety are disruptive symptoms in breast cancer survivors; however, little is known about these symptoms in postmenopausal breast cancer survivors on aromatase inhibitors therapies. This study aimed to determine the relationship between anxiety and vaginal-related sexual health problems in this population. METHODS: We analyzed cross-sectional data from a cohort study of postmenopausal women breast cancer survivors receiving aromatase inhibitors. Vaginal-related sexual health problems were assessed with the Breast Cancer Prevention Trial Symptom Checklist. Anxiety was assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale. We used multivariable logistic regression to evaluate relationship between anxiety and vaginal-related sexual health adjusted for clinical and sociodemographic variables. RESULTS: Among 974 patients, 305 (31.3%) reported anxiety and 403 (41.4%) had vaginal-related sexual health problems. Compared to those without anxiety, patients with borderline and clinically abnormal anxiety reported higher rates of vaginal-related sexual health problems (36.8% vs. 49% and 55.7% respectively, p < 0.001). In multivariate analyses adjusted for clinical and sociodemographic factors, abnormal anxiety was associated with a higher rate of vaginal-related sexual health problems, with adjusted odds ratios of 1.69 (95% CI 1.06-2.70, p = 0.03). Vaginal-related sexual health problems were more frequent among patients who were under 65 years of age, received Taxane-based chemotherapy, reported depression, and were married/living with a partner (p < 0.05). CONCLUSION: Among postmenopausal breast cancer survivors on aromatase inhibitors therapies, anxiety was significantly associated with vaginal-related sexual health problems. As treatments for sexual health problems are limited, results suggest that psychosocial interventions for anxiety could potentially be adapted to simultaneously address sexual health needs.

Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with chemotherapy, but researchers rarely study its risk factors, fall risk, and prevalence in long-term breast cancer survivors. We aimed to determine CIPN prevalence, risk factors, and association with psychological distress and falls among long-term breast cancer survivors. We conducted Cross-sectional analyses among postmenopausal women with a history of stage I-III breast cancer who received taxane-based chemotherapy. Participants reported neuropathic symptoms of tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We conducted multivariate logistic regression analyses to evaluate risk factors associated with the presence of CIPN and the relationship between CIPN and anxiety, depression, insomnia, and patient-reported falls. Among 296 participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with women of normal weight, being obese was associated with increased risk of CIPN (adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater insomnia severity, anxiety, and depression than those without (all p < 0.05). Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and 41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively, experiencing falls (p = 0.028). The majority of long-term breast cancer survivors who received taxane-based chemotherapy reported CIPN symptoms; obesity was a significant risk factor. Those with CIPN also reported increased psychological distress and falls. Interventions need to target CIPN and comorbid psychological symptoms, and incorporate fall prevention strategies for aging breast cancer survivors.

Arthralgia among women taking aromatase inhibitors: is there a shared inflammatory mechanism with co-morbid fatigue and insomnia?

INTRODUCTION: Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs. METHODS: Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations. RESULTS: Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (ß = 93.1; 95 % confidence interval (CI): 25.1-161.1; p = 0.008), eotaxin (ß = 79.9; 95 % CI: 32.5-127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (ß = 151.2; 95 % CI: 32.7-269.8; p = 0.013), and vitamin D-binding protein (VDBP) (ß = 19,422; 95 % CI: 5500.5-33,344; p = 0.006). CONCLUSIONS: Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.

Do attitudes and beliefs regarding complementary and alternative medicine impact its use among patients with cancer? A cross-sectional survey.

BACKGROUND: Complementary and alternative medicine (CAM) incorporates treatments used by cancer survivors in an attempt to improve their quality of life. Although population studies have identified factors associated with its use, to the best of the authors knowledge, assessment of why patients use CAM or the barriers against its use have not been examined to date. METHODS: The authors conducted a cross-sectional survey study in the thoracic, breast, and gastrointestinal medical oncology clinics at an academic cancer center. Clinical and demographic variables were collected by self-report and chart abstraction. Attitudes and beliefs were measured using the validated Attitudes and Beliefs about CAM (ABCAM) instrument. This instrument divides attitudes and beliefs into 3 domains: expected benefits, perceived barriers, and subjective norms. RESULTS: Among 969 participants (response rate, 82.7%) surveyed between June 2010 and September 2011, patient age ≤65 years, female sex, and college education were associated with a significantly greater expected benefit from CAM (P<.0001 for all). Nonwhite patients reported more perceived barriers to CAM use compared with white patients (P<.0001), but had a similar degree of expected benefit (P = .76). In a multivariate logistic regression analysis, all domains of the ABCAM instrument were found to be significantly associated with CAM use (P<.01 for all) among patients with cancer. Attitudes and beliefs regarding CAM explained much more variance in CAM use than clinical and demographic variables alone. CONCLUSIONS: Attitudes and beliefs varied by key clinical and demographic characteristics, and predicted CAM use. By developing CAM programs based upon attitudes and beliefs, barriers among underserved patient populations may be removed and more patient centered care may be provided.

Black breast cancer survivors experience greater upper extremity disability.

Over one-third of breast cancer survivors experience upper extremity disability. Black women present with factors associated with greater upper extremity disability, including: increased body mass index (BMI), more advanced disease stage at diagnosis, and varying treatment type compared with Whites. No prior research has evaluated the relationship between race and upper extremity disability using validated tools and controlling for these factors. Data were drawn from a survey study among 610 women with stage I-III hormone receptor positive breast cancer. The disabilities of the arm, shoulder and hand (QuickDASH) is an 11-item self-administered questionnaire that has been validated for breast cancer survivors to assess global upper extremity function over the past 7 days. Linear regression and mediation analysis estimated the relationships between race, BMI and QuickDASH score, adjusting for demographics and treatment types. Black women (n = 98) had 7.3 points higher average QuickDASH scores than White (n = 512) women (p < 0.001). After adjusting for BMI, age, education, cancer treatment, months since diagnosis, and aromatase inhibitor status, Black women had an average 4-point (95 % confidence interval 0.18-8.01) higher QuickDASH score (p = 0.04) than White women. Mediation analysis suggested that BMI attenuated the association between race and disability by 40 %. Even several years post-treatment, Black breast cancer survivors had greater upper extremity disability, which was partially mediated by higher BMIs. Close monitoring of high BMI Black women may be an important step in reducing disparities in cancer survivorship. More research is needed on the relationship between race, BMI, and upper extremity disability.

Attitudes and barriers towards participation in an acupuncture trial among breast cancer patients: a survey study.

BACKGROUND: As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify socio-demographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients. METHODS: We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center. RESULTS: Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p < 0.001), and previous radiation therapy (p = 0.004) were significantly associated with WTP. Travel difficulty (p = 0.002), concern with experimentation (p = 0.013), and lack of interest in acupuncture (p < 0.001) were significant barriers to WTP. Barriers differed significantly by socio-demographic factors with white people more likely to endorse travel difficulty (p = 0.018) and non-white people more likely to report concern with experimentation (p = 0.024). Older patients and those with lower education were more likely to report concern with experimentation and lack of interest in acupuncture (p < 0.05). CONCLUSIONS: Although nearly half of the respondents reported WTP, significant barriers to participation exist and differ among subgroups. Research addressing these barriers is needed to ensure effective accrual and improve the representation of individuals from diverse backgrounds.

Association between Hispanic Ethnicity and Greater Expectation of Benefit from Acupuncture or Massage for Pain in Cancer.

Individuals living with cancer and survivors of cancer who self-identify as Hispanic experience higher pain burden and greater barriers to pain management compared with their non-Hispanic counterparts. The Society for Integrative Oncology-ASCO guideline recommends acupuncture and massage for cancer pain management. However, Hispanic individuals' expectations about these modalities remain under-studied and highlight a potential barrier to treatment utilization in this population. We conducted a subgroup analysis of baseline data from two randomized clinical trials to evaluate ethnic differences in treatment expectations about integrative pain treatment modalities among Hispanic and non-Hispanic cancer patients and survivors of cancer. The Mao Expectancy of Treatment Effects (METE) instrument was used to measure treatment expectancy for electro-acupuncture, auricular acupuncture, and massage therapy. Results of this study demonstrated that Hispanic participants reported greater expectation of benefit from electroacupuncture, auricular acupuncture, and massage (all P < 0.01). After controlling for age, gender, race, and education, Hispanic ethnicity remained significantly associated with greater expectation of benefit from integrative therapies for pain (coef.=1.47, 95% CI, 0.67-2.27). Non-white race (coef.=1.04, 95% CI, 0.42-1.65), no college education (coef.=1.16, 95% CI, 0.59-1.74), and female gender (coef.=0.94, 95% CI, 0.38-1.50) were also associated with a greater expectation of benefit from integrative therapies. Pain management should be informed by a shared decision-making approach that aligns treatment expectancy with treatment selections to optimize outcomes. Compared with non-Hispanic participants, Hispanic individuals reported higher expectation of benefit from acupuncture and massage, highlighting the potential role for integrative therapies in addressing ethnic pain disparities. Trial Registration NCT02979574 NCT04095234.

Addressing cancer-related fatigue through sleep: A secondary analysis of a randomized trial comparing acupuncture and cognitive behavioral therapy for insomnia.

Background: Fatigue is a troublesome symptom in cancer survivors that often results from disrupted sleep. We sought to assess whether two insomnia-focused non-pharmacological interventions are also effective for improving fatigue. Methods: We analyzed data from a randomized clinical trial comparing cognitive behavioral therapy for insomnia (CBT-I) versus acupuncture for insomnia among cancer survivors. Participants were 109 patients who reported insomnia and moderate or worse fatigue. Interventions were delivered over eight weeks. Fatigue was evaluated at baseline, week 8, and week 20 using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). We used both mediation analysis and t-tests to explore the extent to which fatigue reduction was attributable to insomnia response. Results: Compared to baseline, both CBT-I and acupuncture produced significant reductions in total MFSI-SF scores at week 8 (-17.1 points; 95% confidence interval [CI]: -21.1 to -13.1, and -13.2 points; 95% CI: -17.2 to -9.2, respectively, all p<0.001) and week 20 (-14.6 points; 95% CI: -18.6 to -10.6, and -14.2 points; 95% CI: -18.1 to -10.3. respectively, all p<0.001), with no significant between-group differences. MFSI-SF total scores at week 8 were significantly associated with sleep improvements in both CBT-I and acupuncture groups (p<0.001 and p=0.011, respectively). Insomnia responders demonstrated significantly greater improvements in mean MFSI-SF total scores compared with non-responders in the CBT-I group (p=0.016) but not in the acupuncture group. Conclusion: CBT-I and acupuncture produced similar, clinically meaningful, and durable fatigue reductions in cancer survivors with insomnia, primarily through improvements in sleep. Acupuncture may also reduce fatigue through additional pathways.

Does expectancy affect insomnia treatment response in cancer survivors receiving acupuncture and cognitive behavioral therapy?

PURPOSE: Insomnia negatively affects quality of life in cancer survivors. Expectations of insomnia treatment efficacy may influence response to intervention. We sought to determine whether pre-treatment outcome expectancy predicts response to two non-pharmacological interventions for insomnia among cancer survivors. METHODS: We analyzed data from a randomized clinical trial that compared acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) in cancer survivors. Patient expectancy was measured by the Mao Treatment Expectancy Scale (MTES) at baseline. Insomnia severity was assessed using the Insomnia Severity Index (ISI) at treatment completion (week 8). Multivariate linear regression was used to evaluate the associations between pre-treatment expectancy and ISI score at week, 8 adjusting for co-variates. RESULTS: Expectancy for acupuncture and CBT-I were similar at baseline (acupuncture: 13.3 ± 4.0; CBT-I: 13.2 ± 2.9, p = 0.17). Greater baseline expectancy scores were associated with a greater and statistically significant insomnia severity reduction at week 8 in the acupuncture group (beta coefficients [Coef.] = - 0.35, 95% confidence interval [CI] = - 0.6 to - 0.1, p = 0.016) adjusted for co-variates. Baseline expectancy was not statistically associated with insomnia severity reduction in the CBT-I group (Coef. = - 0.2, 95% CI = - 0.7 to 0.2, p = 0.31). High expectancy was significantly associated with greater proportion of treatment responders at week 8 in the acupuncture group (76% vs. 38%, p = 0.001) but not in the CBT-I group (83% vs. 70%, p = 0.21). CONCLUSIONS: Higher pre-treatment outcome expectancy predicted significantly greater insomnia improvement in patients receiving acupuncture but not in those receiving CBT-I. IMPLICATIONS FOR CANCER SURVIVORS: Aligning treatment provision with expected outcomes may lead to personalized non-pharmacological insomnia management for cancer survivors.

Impact of Baseline Expectancy on Outcome Prediction of Real and Sham Acupuncture for Persistent Chemotherapy-Induced Peripheral Neuropathy Pain in Solid Tumor Survivors: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) pain significantly worsens cancer survivors' quality of life. Expectancy may play an important role in acupuncture response. We sought to explore whether expectancy predicts pain outcome in real acupuncture (RA) and sham acupuncture (SA) in cancer survivors. METHODS: We analyzed data from a randomized clinical trial that evaluated the effect of RA on CIPN symptoms compared to SA and wait list control (WLC) in 75 cancer survivors. This secondary analysis was limited to CIPN pain measured by the Numeric Rating Scale (NRS), graded from 0 to 10. Interventions were delivered over 8 weeks. SA was implemented using a combination of non-acupuncture points and a non-insertion procedure. Patient expectancy was measured by the Acupuncture Expectancy Scale (AES) 3 times during the study. We used a linear regression model to evaluate if the NRS score was associated with the baseline AES score at the end of treatment (week 8), adjusting for baseline NRS score. RESULTS: AES was similar among 3 groups at baseline (RA: 11.8 ± 2.7; SA: 12.1 ± 3.8.; WLC: 14.6 ± 4.2; P = .062). Baseline AES was not found to be significantly associated with the week 8 NRS score among patients in all RA, SA, and WLC groups (all P > .05). However, we found a trend that higher baseline AES predicted lower NRS score at week 8 in the SA group: a one-point higher score on baseline expectancy was associated with a 0.3-point reduction in NRS pain score (P = .059) at week 8. CONCLUSIONS: The association of baseline expectancy and acupuncture response was similar between RA and SA. However, SA seemed to rely more on expectancy than RA. Further studies with larger sample sizes are needed to confirm this finding.

Comparing sleep measures in cancer survivors: Self-reported sleep diary versus objective wearable sleep tracker.

Purpose: Cancer survivors are increasingly using wearable fitness trackers, but it's unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group. Methods: We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB) and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon Singed Ranks Test, Spearman's rank correlation coefficients, and the Mann-Whitney Test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data. Results: Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but Fitbit outcomes didn't. Conclusions: TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.

Development and Validation of an Instrument for Measuring Attitudes and Beliefs about Complementary and Alternative Medicine (CAM) Use among Cancer Patients.

Despite cancer patients' extensive use of complementary and alternative medicine (CAM), validated instruments to measure attitudes, and beliefs predictive of CAM use are lacking. We aimed at developing and validating an instrument, attitudes and beliefs about CAM (ABCAM). The 15-item instrument was developed using the theory of planned behavior (TPB) as a framework. The literature review, qualitative interviews, expert content review, and cognitive interviews were used to develop the instrument, which was then administered to 317 outpatient oncology patients. The ABCAM was best represented as a 3-factor structure: expected benefits, perceived barriers, and subjective norms related to CAM use by cancer patients. These domains had Eigenvalues of 4.79, 2.37, and 1.43, and together explained over 57.2% of the variance. The 4-item expected benefits, 7-item perceived barriers, and 4-item subjective norms domain scores, each had an acceptable internal consistency (Cronbach's alpha) of 0.91, 0.76, and 0.75, respectively. As expected, CAM users had higher expected benefits, lower perceived barriers, and more positive subjective norms (all P < 0.001) than those who did not use CAM. Our study provides the initial evidence that the ABCAM instrument produced reliable and valid scores that measured attitudes and beliefs related to CAM use among cancer patients.

Tibetan Herbal Pain-Relieving Plaster for Chronic Musculoskeletal Pain Among Cancer Survivors: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled Trial.

Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch (Tibetree Pain-Relieving Plaster, Tibet Cheezheng Tibetan Medicine Co. Ltd., Tibet, China) or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2-7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.

Acupuncture versus cognitive behavioral therapy for pain among cancer survivors with insomnia: an exploratory analysis of a randomized clinical trial.

Pain and insomnia often co-occur and impair the quality of life in cancer survivors. This study evaluated the effect of acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) on pain severity among cancer survivors with comorbid pain and insomnia. Using data from the CHOICE trial that compared acupuncture versus CBT-I for insomnia among cancer survivors, we analyzed the effect of interventions on pain outcomes in 70 patients with moderate to severe baseline pain. Interventions were delivered over eight weeks. We assessed average pain severity (primary outcome) and pain interference at baseline, week 8, and week 20. We further defined insomnia and pain responders as patients who achieved clinically meaningful improvement in insomnia and pain outcomes, respectively, at week 8. We found that compared with baseline, the between-group difference (-1.0, 95% CI -1.8 to -0.2) was statistically significant favoring acupuncture for reduced pain severity at week 8 (-1.4, 95% CI -2.0 to -0.8) relative to CBT-I (-0.4, 95% CI-1.0 to 0.2). Responder analysis showed that 1) with acupuncture, insomnia responders reported significantly greater pain reduction from baseline to week 4, compared with insomnia non-responders (-1.5, 95% CI -2.7 to -0.3); 2) with CBT-I, pain responders reported significantly greater insomnia reduction at week 8, compared with pain non-responders (-4.7, 95% CI -8.7 to -1.0). These findings suggest that among cancer survivors with comorbid pain and insomnia, acupuncture led to rapid pain reductions, which contributed to a decrease in insomnia, whereas CBT-I had a delayed effect on pain, possibly achieved by insomnia improvement.

Tibetan herbal pain-relieving plaster for low back pain: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan traditional medicine CheeZheng Pain-Relieving Plaster (CZPRP) is frequently used as an over-the-counter external analgesic for musculoskeletal pain; however, its evidence for low back pain (LBP) has not been evaluated. AIM OF THE STUDY: This study aims to assess the efficacy and safety of CZPRP for both acute, subacute and chronic LBP through a systematic review and meta-analysis of clinical trials. MATERIALS AND METHODS: PubMed, CENTRAL, CNKI, CQVIP, and Wanfang databases were searched through April 20, 2020 for randomized controlled trials of CZPRP for LBP. Eligible comparators were placebo, active treatment, or usual care. Clinical outcomes included pain severity, lower back function score, pain-free rate, and adverse events (AEs). Qualitative evaluations were conducted using the Cochrane risk of bias assessment tools. Quantitative analyses were conducted using a random-effects model. RESULTS: This study includes 1674 LBP patients from nine clinical studies. Pooled analyses among subjects with acute LBP show 1) significant pain reductions (mean difference -0.84, 95% confidence interval[CI] -1.31, -0.37) in CZPRP plus diclofenac versus diclofenac, 2) significant improvements in lower back function (standard mean difference -1.50, 95% CI -2.16, -0.85) in CZPRP versus diclofenac, and 3) a higher pain-free rate in CZPRP alone (risk ratio 1.48, 95% CI 1.16, 1.89; I2 = 61%) or CZPRP plus nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio 1.66, 95% CI 1.14, 2.40; I2 = 0%) versus NSAIDs. However, in a heterogeneous population with mixed LBP subtypes, there was no significant difference in pain outcomes between CZPRP and diclofenac. Additionally, CZPRP use did not increase AEs compared with no CZPRP (p = 0.40). All nine studies are associated with moderate to high risk of bias. CONCLUSIONS: The use of CZPRP is associated with improved acute LBP outcomes compared to diclofenac. However, due to the moderate to high risk of bias of the studies, future rigorous randomized controlled trials are needed to evaluate the effects of CZPRP for acute and chronic LBP.

A Systematic Review of CheeZheng Pain Relieving Plaster for Musculoskeletal Pain: Implications for Oncology Research and Practice.

BACKGROUND: Musculoskeletal pain is a common and debilitating condition for cancer patients. Existing therapies for these pain conditions have substantial limitations. To identify an integrative approach to pain management, we conducted a systematic review to evaluate the safety and efficacy of a Tibetan herbal-based topical agent, CheeZheng Pain Relieving Plaster (PRP), for the treatment of osteoarthritis (OA) pain. METHODS: We extracted citations from PubMed and Chinese databases (CNKI, WanFang Data, and CQVIP). We included randomized clinical trials evaluating the effectiveness and safety of CheeZheng PRP compared to conventional OA pain treatments. RESULTS: Twenty-two randomized clinical trials (n = 2556 participants) compared CheeZheng PRP against nonsteroidal anti-inflammatory drugs (11), glucosamine (2), intraarticular corticosteroid (2), hyaluronic acid injections (6), and acetaminophen (1). Ten studies found a statistically greater effectiveness (assessed by ≥30% reduction in symptom severity) of CheeZheng PRP in improving OA pain (measured by the Visual Analogue Scale), stiffness, and function compared to control. Ten studies reported that 4.8% of participants experienced application site skin irritation that resolved after discontinuing the plaster. Randomization was not sufficiently described in most studies, and no placebo-controlled trials were identified. CONCLUSIONS: There is promising evidence for the safety and clinical effectiveness of CheeZheng PRP to treat OA; however, lack of placebo control and unclear descriptions of randomization increase the potential risk for bias. Future randomized, placebo-controlled trials are needed to establish the safety and efficacy of CheeZheng PRP for pain management in oncology settings.

Acupuncture versus medication for pain management: a cross-sectional study of breast cancer survivors.

AIM OF THE STUDY: Breast cancer survivors who take aromatase inhibitors (AI) often suffer from chronic pain. Emerging evidence supports the use of acupuncture as an effective pain management strategy for this condition, but its acceptability among cancer survivors is unknown. We evaluated breast cancer survivors' preferences for acupuncture as compared with medication use and identified factors predictive of this preference. METHODS: We conducted a cross-sectional study among breast cancer survivors who were currently, or had been, taking an AI. The primary outcome was degree of preference for acupuncture as compared with medication for pain management. We conducted multivariate logistic regression analyses to evaluate the effects of socioeconomic status (SES) factors and health beliefs on treatment preference. RESULTS: Among 592 participants, 160 (27.0%) preferred acupuncture, 153 (25.8%) preferred medication and 279 (47.1%) had no clear preference. In a multivariate analysis that only included SES, higher education and white race were significantly associated with greater preference for acupuncture. When health beliefs were added, SES effects were attenuated, while greater expectation of acupuncture's effect, lower perceived barriers to its use, higher social norm (endorsement from family members and healthcare professionals) related to acupuncture and higher holistic health beliefs were associated with greater preference for acupuncture. CONCLUSION: We found similar rates of preference for acupuncture versus medication among breast cancer survivors for pain management. Specific attitudes and beliefs predicted such preferences, highlighting the importance of a patient-centred approach to align patient beliefs and preferences with therapeutic options for more effective pain management. TRIAL REGISTRATION NUMBER: NCT01013337; Results.

Comparison of cytochrome P450 inhibition assays for drug discovery using human liver microsomes with LC-MS, rhCYP450 isozymes with fluorescence, and double cocktail with LC-MS.

The disparity of IC(50)s from CYP450 inhibition assays used to assess drug-drug interaction potential was investigated, in order to have evidence for selecting a reliable in vitro CYP450 inhibition assay to support drug discovery. Three assays were studied: individual rhCYP isozymes and corresponding coumarin derivative-probe substrates with fluorescent detection, human liver microsomes (HLM) and cocktail drug-probe substrates with LC-MS detection, and double cocktail rhCYP isozymes mix and drug-probe mix with LC-MS detection. Data comparisons showed that the rhCYP-fluorescent assay and the cocktail assay with HLM-LC-MS had weak correlation. Detection method and probe substrates were shown to not be the major cause of the disparity in IC(50)s. However, the enzyme source and composition (HLM versus, rhCYP) caused disparity in IC(50)s. Specifically, the high concentrations of CYP isozymes often used with HLM-based assays produced high probe substrate conversion and test compound metabolism, which should both contribute to artificially higher IC(50)s. Non-specific binding of substrate to higher concentration proteins and lipids in the HLM-based assays should also contribute to higher IC(50)s. The modified double cocktail assay was found to overcome limitations of the other two assays. It uses an rhCYP isozymes mix, drug-probe substrate mix, low protein concentration, and LC-MS detection. The double cocktail assay is sensitive, selective, and high throughout for use in drug discovery to provide an early alert to potential toxicity with regard to drug-drug interaction, prioritize chemical series, and guide structural modification to circumvent CYP450 inhibition.

High throughput microsomal stability assay for insoluble compounds.

High throughput metabolic stability assays are widely implemented in drug discovery to guide structural modification, predict in vivo performance, develop structure-metabolic stability relationships, and triage compounds for in vivo animal studies. However, these methods are often developed and validated using commercial drugs. Many drug discovery compounds differ from commercial drugs, with many having high lipophilicity, high molecular weight and low solubility. The impact of very low solubility on metabolic stability assay results was explored. Two metabolic stability assays, the 'aqueous dilution method' and the 'cosolvent method, were compared. For commercial drugs and most discovery compounds having reasonable drug-like properties, the two methods gave comparable results. For highly lipophilic, insoluble drug discovery compounds, the 'aqueous dilution method' gave artificially higher stability results. The cosolvent method performs compound dilutions in solutions with higher organic solvent content and adds solutions directly to microsomes to assist with solubilization, minimize precipitation and reduce non-specific binding to plastics. This method is more applicable in drug discovery where compounds of a wide range of solubility are studied.