Double-blinding of an acupuncture randomized controlled trial optimized with clinical translational science award resources.

BACKGROUND: Clinical trial articles often lack detailed descriptions of the methods used to randomize participants, conceal allocation, and blind subjects and investigators to group assignment. We describe our systematic approach to implement and measure blinding success in a double-blind phase 2 randomized controlled trial testing the efficacy of acupuncture for the treatment of vulvodynia. METHODS: Randomization stratified by vulvodynia subtype is managed by Research Electronic Data Capture software's randomization module adapted to achieve complete masking of group allocation. Subject and acupuncturist blinding assessments are conducted multiple times to identify possible correlates of unblinding. RESULTS: At present, 48 subjects have been randomized and completed the protocol resulting in 87 subject and 206 acupuncturist blinding assessments. DISCUSSION: Our approach to blinding and blinding assessment has the potential to improve our understanding of unblinding over time in the presence of possible clinical improvement.

Vulvodynia, "A Really Great Torturer": A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies.

BACKGROUND: Women with vulvodynia, a chronic pain condition, experience vulvar pain and dyspareunia. Few studies examine the range and combination of treatment strategies that women are actually using to reduce vulvodynia. AIM: To describe pain experiences and pain relief strategies of women with vulvodynia. METHODS: Convenience sample, 60 women with vulvodynia (median age 32.5 [interquartile range {IQR} 8.5] years; 50 white, 10 racial/ethnic minorities) completed PAINReportIt and reported use of drugs and alcohol and responded to open-ended questions. Univariate descriptive statistics and bivariate inferential tests were used to describe average pain intensity scores, alcohol use, smoking, number of pain relief strategies, and their associations. Women's open-ended responses about their pain experiences and drug and non-drug pain relief strategies (NDPRS) were analyzed for patterns. OUTCOMES: Our mixed methods analysis connected data from pain measures, prescribed treatments and self-reported behaviors with women's free responses. This enabled nuanced insights into women's vulvodynia pain experiences. RESULTS: Women's descriptions of their pain and suffering aligned with their reported severe pain and attempts to control their pain, with a median pain intensity of 6.7 (IQR 2.0) despite use of adjuvant drugs (median 2.0 [IQR 2.0]), and opioids (median 1.0 [IQR 2.0]). 36 women (60%) used alcohol to lessen their pain. 26 women (43%) listed combining analgesics and alcohol to relieve their pain. 30 women (50%) smoked cigarettes. 54 women (90%) used ≥1 NDPRS. The mean number of NDPRS used was 2.1 ± 1.3 (range 0-6). The 5 most common NDPRS from women's comments were herbal medicine (40%), acupuncture (27%), massage (22%), hypnosis (15%), and mental healthcare (13%). CLINICAL IMPLICATIONS: Severe pain in women with vulvodynia may be a clinical indicator of those at higher risk of combining prescription pain medications with alcohol, which are all central nervous system depressants and may potentiate overdose. STRENGTHS AND LIMITATIONS: This pilot study demonstrated that the mixed methods approach to help understand the complexity of vulvodynia was feasible. We identified data showing a reliance on a high-risk mix of prescriptions and alcohol to reduce vulvodynia pain and a high prevalence of cigarette smoking. However, as a pilot study, these results are considered preliminary; the sample may not be representative. Perhaps only women at the extreme end of the pain continuum participated, or women took the survey twice because identifiers were not collected. CONCLUSION: Despite attempts to reduce pain using multiple therapies, including alcohol, women's vulvodynia pain is severe and not controlled. Schlaeger JM, Pauls HA, Powell-Roach KL, et al. Vulvodynia, "A Really Great Torturer": A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies. J Sex Med 2019;16:1255-1263.

The effect of neighborhood-level socioeconomic status on racial differences in ovarian cancer treatment in a population-based analysis in Chicago.

BACKGROUND: Less than half of women with ovarian cancer and blacks specifically receive therapy adherent to National Comprehensive Cancer Network (NCCN) guidelines. The purpose is to assess the effect of neighborhood-level socioeconomic status (SES) on black-white treatment differences in a population-based analysis in a highly-segregated community. METHODS: Illinois State Cancer Registry data for invasive epithelial ovarian cancer cases diagnosed in Cook County, IL in non-Hispanic white (NHW) or black (NHB) women from 1998 to 2009 was analyzed. As few women receive NCCN-adherent care, variables were constructed to assess extent of treatment, including receipt of: 1) debulking surgery; 2) any surgery; 3) multi-agent chemotherapy; and 4) any chemotherapy. Two measures (concentrated affluence and disadvantage) were used to estimate neighborhood-level SES. Multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (95% CI), with generalized linear mixed models to account for hierarchical data. RESULTS: 2766 (81.0%) NHW and 647 (19.0%) NHB women were diagnosed. Adjusting for covariates, NHB were less likely to receive debulking surgery (OR: 0.39; 95% CI: 0.30-0.50), any surgery (OR: 0.38; 95%CI: 0.29-0.49), multi-agent chemotherapy (OR: 0.56; 95% CI: 0.45-0.71) and any chemotherapy (OR: 0.58; 95% CI: 0.45-0.74). Concentrated affluence but not disadvantage was significant in final models for multi-agent and any chemotherapy, but not debulking or any surgery. CONCLUSIONS: Results identify black-white differences consistent across treatments that persist despite adjustment for neighborhood-level SES. IMPACT: Results advance inequality awareness beyond "ideal" NCCN-adherent care, indicating inequality exists in delivery of even the most basic oncologic care.

Protocol for double-blind RCT of acupuncture for vulvodynia.

Background: Vulvodynia, vulvar pain of unknown origin lasting at least 3 months, affects 7% of American women. Dyspareunia, its frequent companion, renders sexual intercourse virtually impossible. Although few therapies are efficacious and rapid pain relief is rarely possible, there have been no sham/placebo-controlled studies of acupuncture for vulvodynia. Aims are to: 1) determine efficacy of acupuncture for vulvodynia, 2) explore duration of the acupuncture effect. Methods: In a pretest/posttest randomized controlled, double-blind (practitioner-patient) efficacy trial of a standardized acupuncture protocol, we will randomize 80 participants 1:1 to either penetrating needle or skin-touch placebo needle groups. Both types of needles are designed to blind both the acupuncturist and participant. Participants with vulvodynia will insert and remove a tampon as a standardized stimulus and complete primary measures of vulvar pain (pain intensity) and secondary measures of dyspareunia (Female Sexual Function Index, FSFI dyspareunia subscale score) and sexual function (FSFI total score) pretreatment, after the 10th acupuncture session, and pain measures weekly until return to pretest levels. Upon study completion control group participants will be offered 10 free real acupuncture sessions. Discussion: This is the first multi-needle multi-session RCT using double-blind acupuncture needles as a reliable sham. We hypothesize that controlling for baseline, at posttest there will be statistically significant less vulvar pain and dyspareunia and more sexual function over five weeks in the penetrating needle group compared to the skin touch placebo group. Conclusion: This study is responsive to the need for efficacious pain management for women with vulvodynia.ClinicalTrials.gov Identifier: NCT03364127.

Acupuncture to Improve Symptoms for Stable Angina: Protocol for a Randomized Controlled Trial.

BACKGROUND: Acupuncture has demonstrated physiologic analgesic effects in Chinese patients with stable angina. One proposed mechanism of action for these analgesic effects is the downregulation of M1 macrophages, interleukin 1 beta, interleukin-6, interleukin-18, and tumor necrosis factor alpha. OBJECTIVE: This study aims to test a 10-session, 5-week acupuncture treatment protocol as a complementary therapy for symptoms of stable angina for American patients, who vary from Chinese patients in health care systems and other salient variables. METHODS: We are conducting a randomized controlled trial (RCT) of 69 adults (35 assigned to initial acupuncture and 34 to an attention control condition) with a medically confirmed diagnosis of stable angina, whose pain and associated symptoms have not been controlled to their satisfaction with guideline-directed medical management. Participants in the experimental group will receive a standardized traditional Chinese medicine point prescription. The attention control group will view non-pain-related health education videos over 5 weeks equal to the 10 hours of treatment for the acupuncture group. Participants will complete the McGill Pain Questionnaire and the Seattle Angina Questionnaire-7, as well as have inflammatory cytokines measured at baseline and study completion. The primary outcomes are anginal pain and quality of life. RESULTS: This study has been funded over 2 years by the National Institutes of Health, National Institute for Nursing Research. We are currently recruiting and expect to have initial results by December 2020. CONCLUSIONS: We will generate data on feasibility, acceptability, effect sizes, and protocol revisions for a future fully powered RCT of the protocol. Findings will help determine if patients with persistent ischemic symptoms experience a proinflammatory state and hyperalgesia caused by multiple neural and immune processes not always relieved with medication. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14705.

Sensory pain characteristics of vulvodynia and their association with nociceptive and neuropathic pain: an online survey pilot study.

OBJECTIVES: To evaluate self-reported sensory pain scores of women with generalized vulvodynia (GV) and provoked vestibulodynia (PVD), characterize pain phenotypes, and assess feasibility of using the Internet for recruitment and data collection among women with vulvodynia. METHODS: Descriptive online survey. Data collected using an online survey accessed via a link on the National Vulvodynia Association web site. Convenience sample, 60 women aged 18 to 45 years (mean = 32.7 ± 5.5); 50 white, 2 black/African American, 4 Hispanic/Latino, and 4 Native American/Alaskan Native, diagnosed with vulvodynia, not in menopause. Pain assessment and medication modules from PAINReportlt. RESULTS: Women with GV (n = 35) compared to PVD (n = 25). Estimated mean pain sites (2.5 ± 1.4 vs 2.2 ± 1.0, P = 0.31), mean current pain (8.7 ± 1.4 vs 5.5 ± 4.0, P = 0.0008), worst pain (8.1 ± 1.8 vs 6.1 ± 3.6, P = 0.02), and least pain in the past 24 hours (4.4 ± 1.8 vs 2.0 ± 2.0, P < 0.0001). Average pain intensity (7.1 ± 1.2 vs 4.6 ± 2.9, P = 0.0003) on a scale of 0 to 10, mean number of neuropathic words (8.3 ± 3.6 vs 7.7 ± 5.0), and mean number of nociceptive words (6.9 ± 4 vs 7.5 ± 4.4). Nineteen (54%) women with GV compared to 9 (38%) with PVD were not satisfied with pain levels. CONCLUSION: Women with GV reported severe pain, whereas those with PVD reported moderate to severe pain. Pain quality descriptors may aid a clinician's decisions about whether to prescribe adjuvant drugs vs opioids to women with vulvodynia.

Racial Disparities in Breast Cancer Survival: The Mediating Effects of Macro-Social Context and Social Network Factors.

This study attempts to clarify the associations between macro-social and social network factors and the continuing racial disparities in breast cancer survival. The study improves on prior methodologies by using a neighborhood disadvantage measure that assesses both economic and social disadvantage and an ego-network measurement tool that assesses key social network characteristics. Our population-based sample included 786 breast cancer patients (nHWhite=388; nHBlack=398) diagnosed during 2005-2008 in Chicago, IL. The data included census-derived macro-social context, self-reported social network, self-reported demographic and medically abstracted health measures. Mortality data from the National Death Index (NDI) were used to determine 5-year survival. Based on our findings, neighborhood concentrated disadvantage was negatively associated with survival among nHBlack and nHWhite breast cancer patients. In unadjusted models, social network size, network density, practical support, and financial support were positively associated with 5-year survival. However, in adjusted models only practical support was associated with 5-year survival. Our findings suggested that the association between network size and breast cancer survival is sensitive to scaling of the network measure, which helps to explain inconsistencies in past findings. Social networks of nHWhites and nHBlacks differed in size, social support dimensions, network density, and geographic proximity. Among social factors, residence in disadvantaged neighborhoods and unmet practical support explained some of the racial disparity in survival. Differences in late stage diagnosis and comorbidities between nHWhites and nHBlacks also explained some of the racial disparity in survival. Our findings highlight the relevance of social factors, both macro and inter-personal in the racial disparity in breast cancer survival. Findings suggest that reduced survival of nHBlack women is in part due to low social network resources and residence in socially and economically deprived neighborhoods. To improve survival among breast cancer patients social policies need to continue improving health care access as well as racially patterned social and economic disadvantage.

Examining racial disparities in colon cancer clinical delay in the Colon Cancer Patterns of Care in Chicago study.

PURPOSE: We explored a potential racial disparity in clinical delay among non-Hispanic (nH) Black and White colon cancer patients and examined factors that might account for the observed disparity. METHODS: Patients aged 30-79 years with a newly diagnosed colon cancer from 2010 to 2014 (n = 386) were recruited from a diverse sample of nine public, private, and academic hospitals in and around Chicago. Prolonged clinical delay was defined as 60 days or more or 90 days or more between medical presentation (symptoms or a screen-detected lesion) and treatment initiation (surgery or chemotherapy). Multivariable logistic regression with model-based standardization was used to estimate the disparity as a difference in prevalence of prolonged delay by race. RESULTS: Prevalence of delay in excess of 60 days was 12 percentage points (95% confidence interval: 2%, 22%) higher among nH Blacks versus Whites after adjusting for age, facility, and county of residence. Travel burden (time and distance traveled from residence to facility) explained roughly one-third of the disparity (33%, P = .05), individual and area-level socioeconomic status measures explained roughly one-half (51%, P = .21), and socioeconomic measures together with travel burden explained roughly four-fifths (79%, P = .08). CONCLUSIONS: Low socioeconomic status and increased travel burden are barriers to care disproportionately experienced by nH Black colon cancer patients.

Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia.

BACKGROUND: Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. METHODS: Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. RESULTS: The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/µL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/µL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8-36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5-5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/µL), sex workers (AOR = 0.55; 95% CI, .44-.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34-.57) were significantly less likely to have ART deferred. CONCLUSIONS: Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.