Keys to Recruiting and Retaining Seriously Ill African Americans With Sickle Cell Disease in Longitudinal Studies: Respectful Engagement and Persistence.

OBJECTIVES: Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN: In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS: We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION: Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.

A Stepped-Wedge Randomized Controlled Trial: Effects of eHealth Interventions for Pain Control Among Adults With Cancer in Hospice.

CONTEXT: Unrelieved cancer pain at the end of life interferes with achieving patient-centered goals. OBJECTIVE: To compare effects of usual hospice care and PAINRelieveIt® on pain outcomes in patients and their lay caregivers. METHODS: In a five-step, stepped-wedge randomized, controlled study, 234 patients (49% male, 18% Hispanic, 51% racial minorities) and 231 lay caregivers (26% male, 20% Hispanic, 54% racial minorities) completed pre-pain/post-pain measures. They received usual hospice care with intervention components that included a summary of the patient's pain data, decision support for hospice nurses, and multimedia education tailored to the patient's and lay caregiver's misconceptions about pain. RESULTS: The intervention effect on analgesic adherence (primary outcome) was not significant. Post-test worst pain intensity was significantly higher for the experimental group, but the difference (0.70; CI = [0.12, 1.27]) was not clinically meaningful. There was nearly universal availability of prescriptions for strong opioids and adjuvant analgesics for neuropathic pain in both groups. Lay caregivers' pain misconceptions (0-5 scale) were significantly lower in the experimental group than the usual care group (mean difference controlling for baseline is 0.38; CI = [0.08, 0.67]; P = 0.01). CONCLUSION: This randomized controlled trial was a negative trial for the primary study outcomes but positive for a secondary outcome. The trial is important for clearly demonstrating the feasibility of implementing the innovative set of interventions.

Sensitivities to Thermal and Mechanical Stimuli: Adults With Sickle Cell Disease Compared to Healthy, Pain-Free African American Controls.

Evidence supports, but is inconclusive that sensitization contributes to chronic pain in some adults with sickle cell disease (SCD). We determined the prevalence of pain sensitization among adults with SCD pain compared with pain-free healthy adults. In a cross sectional, single session study of 186 African American outpatients with SCD pain (age 18-74 years, 59% female) and 124 healthy age, gender, and race matched control subjects (age 18-69 years, 49% female), we compared responses to standard thermal (Medoc TSA II) and mechanical stimuli (von Frey filaments). Although we observed no significant differences in thermal thresholds between controls and patients, patients with SCD had lower pain thresholds to mechanical stimuli and reported higher pain intensity scores to all thermal and mechanical stimuli at a non-painful body site. Compared with controls, about twice as many patients with SCD showed sensitization: 12% versus 23% at the anterior forearm site (P = .02), and 16% versus 32% across 3 tested sites (P = .004). Among patients with SCD, 18% exhibited some element of central sensitization. Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD pain experience and should be considered when selecting therapies for SCD pain. PERSPECTIVE: Compared with matched healthy controls, quantitative sensory testing in adults with pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization, including central sensitization. The findings of allodynia and hyperalgesia may indicate neuropathic pain and could contribute to a paradigm shift in assessment and treatment of SCD pain.

Thermal and mechanical quantitative sensory testing values among healthy African American adults.

PURPOSE: Only a few studies have reported quantitative sensory testing (QST) reference values for healthy African Americans, and those studies are limited in sample size and age of participants. The study purpose was to characterize QST values in healthy, pain-free African American adults and older adults whose prior pain experiences and psychological status were also measured. We examined the QST values for differences by sex, age, and body test site. PATIENTS AND METHODS: A cross-sectional sample of 124 pain-free African American adults (age 18-69 years, 49% female) completed demographic and self-reported pain, fatigue and psychosocial measures. QST was performed to obtain thermal and mechanical responses and associated pain intensity levels. RESULTS: We found thermal detection values at the anterior forearm were (29.2 °C±1.6) for cool detection (CD) and (34.5 °C±1.2) for warm detection (WD). At that site the sample had cold pain threshold (CPTh) (26.3 °C±5.0), heat pain threshold (HPTh) (37.8 °C±3.6), and mechanical pain thresholds (MPTH) (16.7±22.2 grams of force, gF). There was a significant between sex difference for WD, with women being more sensitive (q=0.027). Lower body sites were less sensitive than upper body sites across all thermal modalities (q<0.003), but not for the mechanical modality. CONCLUSION: The QST values from this protocol at the anterior forearm indicate that the healthy African American adults had average thermal pain thresholds close to the temperature of adaptation and average MPTh under 20 gF. Differences in responses to thermal and mechanical stimuli for upper verses lower body were consistent with prior research.

Implementing the PAIN RelieveIt Randomized Controlled Trial in Hospice Care: Mechanisms for Success and Meeting PCORI Methodology Standards.

This purpose of this article is to describe how we adhere to the Patient-Centered Outcomes Research Institute's (PCORI) methodology standards relevant to the design and implementation of our PCORI-funded study, the PAIN RelieveIt Trial. We present details of the PAIN RelieveIt Trial organized by the PCORI methodology standards and components that are relevant to our study. The PAIN RelieveIt Trial adheres to four PCORI standards and 21 subsumed components. The four standards include standards for formulating research questions, standards associated with patient centeredness, standards for data integrity and rigorous analyses, and standards for preventing and handling missing data. In the past 24 months, we screened 2,837 cancer patients and their caregivers; 874 dyads were eligible; 223.5 dyads consented and provided baseline data. Only 55 patients were lost to follow-up-a 25% attrition rate. The design and implementation of the PAIN RelieveIt Trial adhered to PCORI's methodology standards for research rigor.

Reproductive health choices for young adults with sickle cell disease or trait: randomized controlled trial immediate posttest effects.

BACKGROUND: People with sickle cell disease (SCD) or sickle cell trait (SCT) may not have information about genetic inheritance needed for making informed reproductive health decisions. CHOICES is a Web-based, multimedia educational intervention that provides information about reproductive options and consequences to help those with SCD or SCT identify and implement an informed parenting plan. Efficacy of CHOICES compared with usual care must be evaluated. OBJECTIVE: The purpose was to compare immediate posttest effects of CHOICES versus an attention-control usual care intervention (e-Book) on SCD-/SCT-related reproductive health knowledge, intention, and behavior. METHODS: In a randomized controlled study, we recruited subjects with SCD/SCT from clinics, community settings, and online networks with data collected at sites convenient to the 234 subjects with SCD (n = 136) or SCT (n = 98). Their ages ranged from 18 to 35 years; 65% were women, and 94% were African American. Subjects completed a measure of sickle cell reproductive knowledge, intention, and behavior before and immediately after the intervention. RESULTS: Compared with the e-Book group, the CHOICES group had significantly higher average knowledge scores and probability of reporting a parenting plan to avoid SCD or SCD and SCT when pretest scores were controlled. Effects on intention and planned behavior were not significant. The CHOICES group showed significant change in their intention and planned behavior, whereas the e-Book group did not show significant change in their intention, but their planned behavior differed significantly. DISCUSSION: Initial efficacy findings are encouraging but warrant planned booster sessions and outcome follow-ups to determine sustained intervention efficacy on reproductive health knowledge, intention, and actual behavior of persons with SCD/SCT.

RNAi: gene-silencing in therapeutic intervention.

Several rapidly developing RNA interference (RNAi) methodologies hold the promise to selectively inhibit gene expression in mammals. RNAi is an innate cellular process activated when a double-stranded RNA (dsRNA) molecule of greater than 19 duplex nucleotides enters the cell, causing the degradation of not only the invading dsRNA molecule, but also single-stranded (ssRNAs) RNAs of identical sequences, including endogenous mRNAs. As such, RNAi technology is currently being evaluated not only as an extremely powerful instrument for functional genomic analyses, but also as a potentially useful method to develop highly specific dsRNA based gene-silencing therapeutics.