by
Erika A. Tyburski;
Scott E. Gillespie;
William A. Stoy;
Robert G. Mannino;
Alexander J. Weiss;
Alexa F. Siu;
Rayford H. Bulloch;
Karthik Thota;
Anyela Cardenas;
Wilena Session;
H Jean Khoury;
Siobhán O’Connor O’Connor;
Silvia Bunting;
Jeanne Boudreaux;
Craig R. Forest;
Manila Gaddh;
Traci Leong;
L. Andrew Lyon;
Wilbur Lam
BACKGROUND: Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels.
METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying degrees and etiologies and compared hematology analyzer Hgb levels with POC Hgb levels, which were estimated via visual interpretation using a color scale and an optional smartphone app for automated analysis.
RESULTS. POC Hgb levels correlated with hematology analyzer Hgb levels (r = 0.864 and r = 0.856 for visual interpretation and smartphone app, respectively), and both POC test methods yielded comparable sensitivity and specificity for detecting any anemia (n = 178) (<11 g/dl) (sensitivity: 90.2% and 91.1%, specificity: 83.7% and 79.2%, respectively) and severe anemia (n = 10) (<7 g/dl) (sensitivity: 90.0% and 100%, specificity: 94.6% and 93.9%, respectively).
CONCLUSIONS. These results demonstrate the feasibility of this POC color-based diagnostic test for self-screening/self-monitoring of anemia.
TRIAL REGISTRATION. Not applicable.
Light microscopy provides a simple, cost-effective, and vital method for the diagnosis and screening of hematologic and infectious diseases. In many regions of the world, however, the required equipment is either unavailable or insufficiently portable, and operators may not possess adequate training to make full use of the images obtained. Counterintuitively, these same regions are often well served by mobile phone networks, suggesting the possibility of leveraging portable, camera-enabled mobile phones for diagnostic imaging and telemedicine. Toward this end we have built a mobile phone-mounted light microscope and demonstrated its potential for clinical use by imaging P. falciparum-infected and sickle red blood cells in brightfield and M. tuberculosis-infected sputum samples in fluorescence with LED excitation. In all cases resolution exceeded that necessary to detect blood cell and microorganism morphology, and with the tuberculosis samples we took further advantage of the digitized images to demonstrate automated bacillus counting via image analysis software. We expect such a telemedicine system for global healthcare via mobile phone - offering inexpensive brightfield and fluorescence microscopy integrated with automated image analysis - to provide an important tool for disease diagnosis and screening, particularly in the developing world and rural areas where laboratory facilities are scarce but mobile phone infrastructure is extensive.
During vascular injury, platelets adhere to exposed subendothelial proteins, such as collagen, on the blood vessel walls to trigger clot formation. Although the biochemical signalings of platelet-collagen interactions have been well characterized, little is known about the role microenvironmental biomechanical properties, such as vascular wall stiffness, may have on clot formation. To that end, we investigated how substrates of varying stiffness conjugated with the same concentration of Type I collagen affect platelet adhesion, spreading, and activation. Using collagen-conjugated polyacrylamide (PA) gels of different stiffnesses, we observed that platelets do in fact mechanotransduce the stiffness cues of collagen substrates, manifesting in increased platelet spreading on stiffer substrates. In addition, increasing substrate stiffness also increases phosphatidylserine exposure, a key aspect of platelet activation that initiates coagulation on the platelet surface. Mechanistically, these collagen substrate stiffness effects are mediated by extracellular calcium levels and actomyosin pathways driven by myosin light chain kinase but not Rho-associated protein kinase. Overall, our results improve our understanding of how the mechanics of different tissues and stroma affect clot formation, what role the increased vessel wall stiffness in atherosclerosis may directly have on thrombosis leading to heart attacks and strokes, and how age-related increased vessel wall stiffness affects hemostasis and thrombosis.
by
Natoshia R. Cunningham;
Susmita Kashikar-Zuck;
Constance Mara;
Kenneth R. Goldschneider;
Dennis A. Revicki;
Carlton D Dampier;
David D. Sherry;
Lori Crosby;
Adam Carle;
Karon F. Cook;
Esi M. Morgan
Pain behaviors are important indicators of functioning in chronic pain; however, no self-reported pain behavior instrument has been developed for pediatric populations. The purpose of this study was to create a brief pediatric measure of patient-reported pain behaviors as part of the Patient-Reported Outcome Measurement Information System (PROMIS). A pool of 47 candidate items for this measure had been previously developed through qualitative research. In this study, youth with chronic pain associated with juvenile fibromyalgia, juvenile idiopathic arthritis, or sickle cell disease (ages 8-18 years) from 3 pediatric centers completed all 47 candidate items for development of the pain behavior item bank along with established measures of pain interference, depressive symptoms, fatigue, average pain intensity, and pain catastrophizing. Caregivers reported on sociodemographic information and health history. Psychometric properties of the pain behavior items were examined using an item response theory framework with confirmatory factor analysis and examination of differential item functioning, internal consistency, and test information curves. Results were used along with expert consensus and alignment with the adult PROMIS pain behavior items to arrive at an 8-item pediatric pain behavior short form, and all 47 items were retained in a calibrated item bank. Confirmatory factor analysis and correlations with validated measures of pain, pain interference, and psychosocial functioning provided support for the short form's reliability and validity. The new PROMIS pediatric pain behavior scale provides a reliable, precise, and valid measure for future research on pain behavior in school-aged children with chronic pain.
by
Carlton Dampier;
Wally R. Smith;
Hae-Young Kim;
Carrie Greene Wager;
Margaret C. Bell;
Caterina P Minniti;
Jeffrey Keefer;
Lewis Hsu;
Lakshmanan Krishnamurti;
A. Kyle Mack;
Donna McClish;
Sonja M. McKinlay;
Scott T. Miller;
Ifeyinwa Osunkwo;
Phillip Seaman;
Marilyn J. Telen;
Debra L. Weiner
Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.
by
Reginald Tran;
David R Myers;
Jordan Ciciliano;
Elaissa L Trybus Hardy;
Yumiko Sakurai;
Byungwook Ahn;
Yongzhi Qiu;
Robert G Mannino;
Meredith E Fay;
Wilbur Lam
by
Carlton Dampier;
Beth Ely;
Darcy Brodecki;
Camille Coleman;
Leela Aertker;
Jocelyn Andrel Sendecki;
Benjamin Leiby;
Karen Kesler;
Terry Hyslop;
Marie Stuart
Background: The epidemiology of painful episodes in infants and younger children with SCD has not been well studied, particularly for pain managed at home. Procedure: SCD infants identified by newborn screening were enrolled in a longitudinal observational study of pain symptoms requiring parents to report the presence or absence of pain daily. When sickle cell related-pain events occurred, pain occurrence, location, associated symptoms and the treatment provided also were reported. Results: 103 children were enrolled at a median age of 7.2 months; 50 had an SS genotype, 32 SC, 6 SB0thalassemia, and 15 SB+thalassemia. Parents/guardians reported for a median of 3.8 years (range 0.3-7.6 years) assessing pain for a total of 141,197 days, excluding any period of recurrent transfusions, with an additional 28,079 days of missing data (16%). Children had pain reported on 2,288 days (1.6%), representing 768 distinct episodes of pain, of which 108 required hospitalizations (14%). Pain locations and symptoms consistent with dactylitis were most prevalent (80%) in the 0-12 month age group, and became progressively less prevalent thereafter. Group-based trajectory modeling of pain episode or pain day frequency identified several trajectory groups with progressively older ages of peak pain frequency, which included 40-45% of SS/SB0thalassemia and 10-12% of SC/SB+thalassemia children. Conclusions: Pain is relatively infrequent in SCD infants and young children and commonly managed at home. Analyses of longitudinal pain trajectories suggest several different pain trajectories, differing in their frequency, age of onset, and age at peak pain frequency with clinical implications for hydroxyurea management.
Background: Patient diaries and pain scales can capture the course and complications of pain managed at home in children. The Faces Pain Scale-Revised (FPS-R) is a validated scale showing reliability in children, but it has not been validated in children with sickle cell disease (SCD). Objective: The purpose of this study was to evaluate comprehension and usability of an electronic modified version of the FPS-R among pediatric patients with SCD.
Methods: This was a cross-sectional, qualitative study involving in-person interviews with children/adolescents from the USA and their parents/legal guardians. Interviews involved cognitive debriefing and usability testing of the FPS-R.
Results: In total, 22 children with SCD aged 4–17 years participated. Children aged 4–6 were generally unable to demonstrate clear understanding of the FPS-R and its response scale. Overall, children aged ≥7 years understood the instrument and could complete it on the electronic device, although children aged 7–8 often needed assistance from the parent. Children aged 9–17 years were able to read and complete the instrument independently. Most participants considered the electronic device easy to use.
Conclusions: The FPS-R was shown to be a comprehensible and usable pain measure for children aged 7–17 with SCD and to be beneficial for future clinical studies.