Association of Cerebral Hemodynamics and Anemia on Processing Speed in Adults with Sickle Cell Disease.

Background and Purpose: Compared to healthy controls, adult patients with Sickle Cell Disease (SCD) are anemic, and therefore have higher cardiac output and Cerebral Blood Flow (CBF) to maintain brain oxygenation. They also demonstrate comparatively more cognitive deficits due to either overt strokes or silent cerebral ischemia. However, there are few correlative studies between CBF and cognitive deficits, specifically processing speed in SCD. Such studies are important to develop biomarkers of central brain processing and ischemia for diagnosis, prognosis, and evaluating the effectiveness of potential interventions. This pilot cross-sectional study tested the hypotheses that adults with SCD and elevated CBF demonstrate lower central brain processing speed than controls on average and that CBF is inversely correlated with processing speed. Methods: We conducted a pilot cross-sectional study to assess the relation-ships between CBF, central brain processing speed, and hemoglobin levels in asymptomatic adults with SCD and controls from an urban academic medical center. MRI acquisitions at 3T consisted of 2D phase-contrast quantitative arteriograms (Qflow) of the bilateral internal carotid and vertebral arteries and 3D pseudo-continuous arterial spin labeling (pCASL) of the brain. Participants were patients with SCD (hemoglobin [Hb]SS, [Hb] SBetaThal°, or [Hb]SC) aged 22-52 years of African American descent (N=7) or community controls (Hb AA) (n=3). Processing speed was assessed as an in-direct functional marker of ischemia using a recommended test from the NIH Toolbox for Assessment of Neurological and Behavioral Function, the Pattern Comparison Processing Speed Test. t-tests were used to compare means of CBF, hemoglobin, and cognition between SCD patients and healthy controls. Among SCD patients only multivariate correla-tions were used to evaluate relationships between brain perfusion in specific brain regions vs. processing speed and CBF. The significance level was set at p≤0.05. Results: Adults with SCD reported higher CBF compared to healthy con-trols (72.15±28.90 vs. 47.23±12.30 ml/min/100g, p=0.04), and lower hemoglobin concentration (8.64±2.33 vs. 13.33±0.58, p=0.001). Heart rate in SCD patients was higher than in controls (86.29±1.37 vs. 74.00±2.10, p=0.04). Patients with SCD demonstrated lower processing speed (96.14±21.04 vs.123±13.74, p=0.02) than controls. Among adult patients with SCD, perfusion in specific regions of the brain showed an inverse relationship with processing speed, as did whole-brain CBF (p=0.0325). Conclusion: These findings, although from a small sample, lend a degree of validity to the claim that processing speed is slower in people with SCD than in controls and that CBF is significantly higher in SCD patients com-pared to controls. The results also lend credence to the finding that the degree of processing speed deficiencies among adults with SCD is correlated with the degree of elevated CBF, which is known to correspond with the degree of anemia associated with SCD.

Feasibility and Quality Validation of a Mobile Application for Enhancing Adherence to Opioids in Sickle Cell Disease.

Prescription opioid nonadherence, specifically opioid misuse, has contributed to the opioid epidemic and opioid-related mortality in the US. Popular methods to measure and control opioid adherence have limitations, but mobile health, specifically smartphone applications, offers a potentially useful technology for this purpose. We developed, tested, and validated the OpPill application using the Mobile Applications Rating Scale (MARS), a validated tool for assessing the quality of mobile health apps. The MARS contains four scales (range of each scale = 0-4) that rate Engagement, Functionality, Aesthetics, and Information Quality. It also assesses subjective quality, relevance, and overall application impact. Our application was built to be a mobile monitoring and reporting system intended to enhance opioid adherence by collecting data and providing systematic feedback on pain and opioid use. Patients (n = 28) all had one of various SCD genotypes, were ages 19 to 59 years (mean 36.56), 53.6% were female, and 39.3% had completed some college. Patients rated the OpPill application highly on all four scales: Engagement, 3.93 ± 0.73; Functionality, 4.54 ± 0.66; Aesthetics, 3.92 ± 0.81; Information, 3.91 ± 0.87. The majority of patients found the application to be relevant for their care. A total of 96% reported the information within the app was complete, while 4% estimated the information to be minimal or overwhelming. Patients (91.7%) overwhelmingly reported that the quality of information as it pertained to SCD patients was relevant; only 8.3% found the application to be poorly relevant to SCD. Similarly, patients (91.7%) overwhelmingly rated both the application's performance and ease of use positively. The large majority of participants (85.7%) found the application to be interesting to use, while 74% found it entertaining. All users found the application's navigation to be logical and accurate with consistent and intuitive gestural design. We conclude that the OpPill application, specifically targeted to monitor opioid use and pain and opioid behavior in patients with Chronic Non-Cancer Pain, was feasible and rated by SCD patients as easy-to-use using a validated rating tool.

A randomised controlled provider-blinded trial of community health workers in sickle cell anaemia: effects on haematologic variables and hydroxyurea adherence.

Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence-based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU-eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU-eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP-HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6-month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care.

Indirect Economic Burden of Sickle Cell Disease.

OBJECTIVE: This study aimed to quantify the indirect costs of sickle cell disease in the United States. METHODS: Adult patients from a sickle cell disease clinic at an urban academic healthcare system completed an adapted Institute for Medical Technology Assessment Productivity Cost Questionnaire related to the impact of their disorder on absenteeism, presenteeism, ability to contribute through unpaid work outside of employment, and other aspects of life. Additional data were collected from patient records about each participant's genotype, total hemoglobin level, and pain level. RESULTS: Of the 192 individuals, 187 who completed the survey reported experiencing vaso-occlusive crisis pain events during the last year that negatively affected their productivity at work and in daily roles. Three-fourths of respondents reported impairment in their ability to complete everyday tasks, such as caring for children, running errands, doing housework, shopping for groceries, and volunteer (unpaid) work. Only 30% of respondents reported being employed or self-employed. Of those employed, estimated costs of absenteeism and presenteeism attributable to pain events averaged $15 103 per person annually. Estimated total annual losses in unpaid work productivity averaged $3 145 862 for the study respondents and another $2 870 652 for their caregivers. CONCLUSIONS: Sickle cell disease affected the work productivity, nonwork productivity, and the daily lives of adults seen with the disorder in an academic medical center.

Survey of Physician Perspective towards Management of Pain for Chronic Conditions in the Emergency Department.

Sickle cell disease (SCD) pain is often acute-on-chronic, likening it to other chronic acute-on-chronic pain conditions. Pain treatment of SCD was already reported as inadequate prior to the current opioid epidemic, but attitudes underlying treatment were understudied. Understanding these attitudes prior to the current epidemic would be revealing. Therefore in 1997, before the current opioid epidemic, we surveyed physicians' attitudes toward pain management and treatment preferences for acute pain exacerbations in the Emergency Department in SCD versus those of chronic pancreatitis and chronic low back pain, two other acute-on-chronic pain diseases. Thirty-nine residency trainees were surveyed in a level one triage hospital. Resident estimates of the rate of opioid addiction in SCD were higher than estimates in both chronic pancreatitis and chronic low back pain. Most residents relied on their personal clinical experience rather than external sources of data or knowledge as the most important driver when they managed chronic pain. This survey research shows that, predating the current opioid epidemic, there was both a backdrop of opioid-phobia and a bias against treating SCD pain compared to other chronic pain conditions among our sample. Repeating this survey research among current training physicians, along with surveys of other attitudes, would provide useful comparisons.