Gamified versus non-gamified online educational modules for teaching clinical laboratory medicine to first-year medical students at a large allopathic medical school in the United States.

BACKGROUND: Medical educators seek innovative ways to engage learners efficiently and effectively. Gamification has been explored as one way to accomplish this feat; however, questions remain about which contexts gamification would be most useful. Time constraints and student interest present major barriers for teaching laboratory medicine to students. This study aims to compare two versions of an interactive online module, one gamified and one not, for teaching laboratory medicine concepts to pre-clinical medical students. METHODS: First-year medical students reviewed either a gamified or non-gamified version of an interactive online module in preparation for an in-person flipped classroom session on Laboratory Medicine. Learning theory guided the design of the modules and both contained identical content, objectives, and structure. The "gamified" module included the additional elements of personalization, progress meters, points, badges, and story/role play. After reviewing the module, students completed an anonymous knowledge check and optional survey. RESULTS: One hundred seventy-one students completed the post module knowledge check as assigned (82 gamified, 89 non-gamified). Knowledge check scores were higher for the students who reviewed the gamified module (p < 0.02), corresponding to an effect size of 0.4 for the gamified module. Eighty-one students completed optional post-module surveys (46 gamified, 35 non-gamified). Instructional efficiency was calculated using task difficulty questions and knowledge check scores, and the resulting instructional efficiency was higher for the gamified module. There was no significant difference in the student-reported time required to complete the modules. Additionally, both versions of the module were well received and led to positive ratings related to motivation and confidence. Finally, examination of open-ended survey results suggested that the addition of game elements added value to the gamified module and enhanced engagement and enjoyment. CONCLUSIONS: In this setting, the addition of gamification to an interactive online module enhanced learning outcome, instructional efficiency, student engagement and enjoyment. These results should inspire further exploration of gamification for teaching Laboratory Medicine concepts to pre-clinical medical students.

Urgent use of voxelotor in sickle cell disease when immediate transfusion is not safe.

The use of blood transfusions to improve anemia resulting from sickle cell disease (SCD) is often limited by alloimmunization, which occurs due to exposure to incompatible antigen present on donor red blood cells (RBCs). This complication occasionally manifests as delayed hemolytic transfusion reactions (DHTRs) that cause hemolysis of the recipient's own RBCs and can lead to fatal anemia. In this case study, we report a patient with SCD who experienced a DHTR following chronic transfusion and was successfully treated with voxelotor, an orally administered sickle hemoglobin (HbS) polymerization inhibitor for the treatment of SCD. Laboratory tests following admission indicated pan-reactivity in antigens, and a rare donor registry was used to locate acceptable units. The patient experienced the DHTR 3 days after admission, which limited laboratory tests due to profound hemolysis. Alternative treatments were limited, and phenotypically matched units were incompatible, so voxelotor was selected as a last-resort treatment. Following initiation of voxelotor 1500 mg, the patient's hemoglobin levels returned to baseline (6 g/dl) within 10 days, with clinical improvements. This report provides evidence regarding the use of voxelotor in the treatment of profound anemia where other treatments could be unsafe or unavailable.

Changes in Mean Corpuscular Volume and RBC Distribution Width Predict Erythrocyte Engraftment Following ABO-Incompatible Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The purpose of this study was to identify laboratory parameters representing erythrocyte engraftment to be used as an indicator to change the recipient to donor ABO group and Rh type following an ABO-incompatible hematopoietic stem cell transplant (HSCT). Studies have shown that ABO incompatibility does not have an effect on outcome of HSCT; however, the serologic consequences of these ABO-incompatible transplants can make it difficult to decide when to begin support with donor ABO/Rh-type blood products. METHODS: This study explored the use of RBC distribution width (RDW), mean corpuscular volume, and hemoglobin as regularly tested laboratory parameters that could be used as surrogate markers for RBC engraftment in 65 patients who received ABO/Rh-incompatible HSCT. RESULTS: The appearance of engrafted donor RBCs correlated with a peak in RDW (P = .002). In addition, our findings suggest that serologic changes in ABO/Rh appear to correspond with a peak in RDW (P = .002). CONCLUSIONS: High values of RDW likely result from a substantial proportion of large, young erythrocytes from recent engraftment with smaller, older pretransplant erythrocytes from the recipient. Our findings suggest that peak RDW may be an indicator of erythrocyte engraftment, following an ABO/Rh-incompatible HSCT.

Prescription Opioid Misuse Index in sickle cell patients: A brief questionnaire to assess at-risk for opioid abuse.

OBJECTIVE: To develop a survey instrument to identify adult sickle cell disease (SCD) patients on chronic opioid therapy who are at-risk for opioid abuse. DESIGN: Prospective survey and interview. SETTING: Adult SCD clinic in a large urban teaching facility. PATIENTS/PARTICIPANTS: Convenience sampling of adult patients presenting to the sickle cell clinic. INTERVENTIONS: None. MAIN OUTCOME: Primary outcome was "at-risk for opioid misuse," defined as at least 3/8 "yes" answers (a positive composite score) on the Prescription Opioid Misuse Index (POMI) questionnaire. Secondary outcome was DSM-IV criteria for substance abuse using the DSM IV Diagnostic Interview Schedule. RESULTS: Of the 99 patients who completed the POMI, the mean age was 36 years; 58.6 percent were female, 48 percent were hemoglobin SS (47/99), and 26 percent were SC (26/99). Twenty-four percent (24/99) were identified as at-risk for opioid misuse using the POMI. There were no differences in demographic, SCD genotype, or socioeconomic variables for at-risk versus not-at-risk patients. CONCLUSION: Twenty-four percent of unselected adult SCD patients on opioids were identified as at-risk for opioid misuse using a quick survey. This may represent as much as 2.5-7 times the national misuse rate. This group of patients may benefit from additional diagnostic and therapeutic interventions to help understand and manage their opioid usage.

Adherence to Recommended Inpatient Hepatic Encephalopathy Workup.

Hepatic encephalopathy (HE) is characterized by altered sensorium and is the most common indication for hospitalization among patients with cirrhosis. Liver societal guidelines for inpatient HE revolve around identification of potential precipitants. In this retrospective study, we aimed to determine adherence to societal guidelines for evaluation of HE in 78 inpatients. The adherence rate to societal recommended guidelines for workup of HE was low, with only 17 (22%) patients having complete diagnostic workup within 24 hours of admission. Notably, 23 (30%) patients were not subjected to blood culture analysis, 16 (21%) were missing urinalysis, and 15 (20%) were missing chest radiograph. In patients with ascites (N = 34), 26 (77%) did not have a diagnostic paracentes is to exclude spontaneous bacterial peritonitis. In contrast, serum ammonia determination, a laboratory test not endorsed by societal guidelines for workup of HE, was ordered in 74 (95%) patients. These findings underscore the limited adherence to societal guidelines in hospitalized patients with HE.

Iron Deficiency Anemia in Patients Undergoing Extracorporeal Photopheresis for Cutaneous T-Cell Lymphoma.

OBJECTIVE: To describe the indicidence and severity of iron deficiency anemia (IDA) in patients who have received extracorporeal photopheresis (ECP) treatment of cutaneous T-cell lymphoma (CTCL). METHODS: We performed a retrospective study during a 9-year period of patients with CTCL who were treated with ECP. ECP was performed with UVAR XTS and CELLEX (Therakos Inc). IDA was defined by a drop in hemoglobin (Hb), mean cell volume (MCV), and increased red blood cell distribution width (RDW). RESULTS: We identified a total of 36 patients; 1 patient was excluded due to severe anemia. In 35 patients, initial hemoglobin values ranged from 9.8 g per dL to 15.9 g per dL, and patients received 4 to 327 ECP treatments. In all, 28 patients showed decreases in Hb of 0.8 g per dL to 6 g per dL during treatments. CONCLUSION: Chronic ECP led to IDA in 28 of 35 patients with CTCL. IDA occurs due to blood loss when ECP equipment does not return full blood volume to patients.

Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES Project.

Background: Pain diary assessment in sickle cell disease (SCD) may be expensive and impose a high respondent burden. Objective: To report whether intermittent assessment could substitute for continuous daily pain assessment in SCD. Design: Prospective cohort study. Setting: Academic and community practices in Virginia. Patients. A total of 125 SCD patients age 16 years or older in the Pain in Sickle Cell Epidemiology Study. Measurements. Using pain measures that summarized all diaries as the gold standard, we tested the statistical equivalence of four alternative strategies that summarized diaries only from the week prior or the month prior to study completion; one week per month; or one day per week (random day). Summary measures included percent pain days, percent crisis days (self-defined), mean pain (0-9 Likert scale) on all days, and mean pain on pain days. Equivalence tests included comparisons of means, regression intercepts, and slopes, as well as measurement of R2. Results: Compared with the gold standard, the one-day-per-week and one-week-per-month strategies yielded statistically equivalent means of six summary pain measures, and the week prior and month prior yielded equivalent means as some of the measures. Regression showed statistically equivalent slopes and intercepts to the gold standard using one-day-per-week and one-week-per-month strategies for percent pain days and percent crisis days, but almost no other equivalence. R2 values ranged from 0.64 to 0.989. Conclusions: It is possible to simulate five- to six-month daily assessment of pain in SCD. Either one-day-per-week or one-week-per-month assessment yields an equivalent mean and fair regression equivalence.

Comorbidity, Pain, Utilization, and Psychosocial Outcomes in Older versus Younger Sickle Cell Adults: The PiSCES Project.

Background. Patients with SCD now usually live well into adulthood. Whereas transitions into adulthood are now often studied, little is published about aging beyond the transition period. We therefore studied age-associated SCD differences in utilization, pain, and psychosocial variables. Methods. Subjects were 232 adults in the Pain in Sickle Cell Epidemiology Study (PiSCES). Data included demographics, comorbidity, and psychosocial measures. SCD-related pain and health care utilization were recorded in diaries. We compared 3 age groups: 16-25 (transition), 26-36 (younger adults), and 37-64 (older adults) years. Results. Compared to the 2 adult groups, the transition group reported fewer physical challenges via comorbidities, somatic complaints, and pain frequency, though pain intensity did not differ on crisis or noncrisis pain days. The transition group utilized opioids less often, made fewer ambulatory visits, and had better quality of life, but these differences disappeared after adjusting for pain and comorbidities. However, the transition group reported more use of behavioral coping strategies. Conclusion. We found fewer biological challenges, visits, and better quality of life, in transition-aged versus older adults with SCD, but more behavioral coping. Further study is required to determine whether age-appropriate health care, behavioral, or other interventions could improve age-specific life challenges of patients with SCD.

Daily home opioid use in adults with sickle cell disease: The PiSCES project.

BACKGROUND: Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. OBJECTIVE: To report on home opioid use among adults with SCD. DESIGN: Cohort study. PARTICIPANTS: Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. MAIN MEASURES: Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. KEY RESULTS: Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. CONCLUSIONS: In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.

Policies and procedures related to testing for weak D phenotypes and administration of Rh immune globulin: results and recommendations related to supplemental questions in the Comprehensive Transfusion Medicine survey of the College of American Pathologists.

CONTEXT: Advances in RHD genotyping offer an opportunity to update policies and practices for testing weak D phenotypes and administration of Rh immune globulin to postpartum women. OBJECTIVES: To repeat questions from a 1999 College of American Pathologists proficiency test survey, to evaluate current practices for testing for weak D and administration of Rh immune globulin, and to determine whether there is an opportunity to begin integrating RHD genotyping in laboratory practice. DESIGN: The College of American Pathologists Transfusion Medicine Resource Committee sent questions from the 1999 survey to laboratories that participated in the 2012 proficiency test survey. The results of the 2012 survey were compared with those from 1999. Results from published RHD genotyping studies were analyzed to determine if RHD genotyping could improve current policies and practices for serological Rh typing. RESULTS: More than 3100 survey participants responded to the 2012 questions. The most significant finding was a decrease in the number of transfusion services performing a serological weak D test on patients as a strategy to manage those with a weak D as Rh negative (from 58.2% to 19.8%, P < .001). Data from RHD genotyping studies indicate that approximately 95% of women with a serological weak D could be managed safely and more logically as Rh positive. CONCLUSIONS: Selective integration of RHD genotyping policies and practices could improve the accuracy of Rh typing results, reduce unnecessary administration of Rh immune globulin in women with a weak D, and decrease transfusion of Rh-negative red blood cells in most recipients with a serological weak D phenotype.

Harvesting autologous stem cells from a patient with red blood cell abnormalities of ß-thalassemia intermedia.

BACKGROUND: Autologous stem cell transplants in patients with hemoglobinopathies are limited. Previous reports used granulocyte-colony-stimulating factor (G-CSF) for mobilization of stem cells; there are no reported cases undergoing plerixafor mobilization. We report such a patient, providing guidance for peripheral blood stem cells collection when aberrant red blood cells (RBCs) disrupt normal separation. STUDY DESIGN AND METHODS: A patient with ß-thalassemia intermedia and hereditary persistence of fetal hemoglobin presented for peripheral blood stem cell collection for autologous transplant for myeloma. He underwent splenectomy for anemia secondary to hemoglobinopathy and chemotherapy, ceasing RBC transfusions. The patient was mobilized using plerixafor after collection with G-CSF failed. RESULTS: Collections were performed using an apheresis system, processing 24 L daily. Peripheral blood and apheresis product CD34 determinations were performed daily. On Day 1, the product yield was 0.04 × 10(6) CD34 cells/kg, less than expected based on white blood cell count and CD34-positive cells. Peripheral blood smear showed nucleated RBCs and RBC morphologic abnormalities. Changes in instrument variables were made after consultation with Terumo BCT to adjust for variable distribution of mononuclear and stem cells during centrifugation. Collecting stem cells at a deeper location and centrifuging faster improved collection, and a cumulative total of 4.40 × 10(6) CD34 cells/kg was achieved after four collections. The patient underwent tandem autologous transplantation and engrafted within 12 to 13 days of each transplant. CONCLUSIONS: Adjustments in apheresis variables allowed successful collection of peripheral blood stem cells from a patient with RBC anomalies of ß-thalassemia that interfered with standard stem cell harvesting.

The HI-STAR study: resource utilization and costs associated with serologic testing for antibody-positive patients at four United States medical centers.

BACKGROUND: Little is known about how the resource utilization and costs of serologic work ups for positive antibody screens vary across subpopulations based on diagnosis, transfusion history, and serologic testing history. STUDY DESIGN AND METHODS: Detailed data were collected on patient demographics, diagnoses, transfusion history, history of known allo- and autoantibodies, and specific serologic tests performed for 6077 consecutive serologic work ups in 3608 antibody-positive patients between 2009 and 2011 at four US academic medical centers. Direct testing costs were also determined at each site for each serologic test performed to calculate total costs per work up and per patient over the duration of the study. RESULTS: The mean direct cost of serologic testing was $114 per work up and $195 per patient. The mean cost per patient was significantly higher for 12 of 19 diagnostic categories evaluated, including autoimmune hemolytic anemia (mean cost per patient, $1490; p < 0.001), hematologic malignancies ($640, p < 0.001), and transplant recipients ($462, p = 0.019). Patient transfusion and serologic testing characteristics associated with greatest increases in costs included history of a warm autoantibody ($626, p < 0.001) and more than five prior transfusions ($404, p < 0.001). CONCLUSION: Antibody-positive patients with complex diagnoses or transfusion histories require significantly more resources and incur greater cost to assess red blood cell antibody status.

Perfluorocarbon emulsion improves oxygen transport of normal and sickle cell human blood in vitro.

Perfluorocarbons (PFC) are compounds with high gas solubility that could help deliver O2 to tissues and have been suggested as adjunct therapy to ischemia. Using a newly designed in vitro system, we tested the hypothesis that a third generation PFC emulsion (Oxycyte) increased O2 transport of blood by measuring changes in O2 extraction ratio. The system included a computer-controlled pump and blood-gas exchange chambers to oxygenate and deoxygenate the blood from nine sickle cell disease (SCD) patients and five healthy donors. The flowing blood reached various levels of hemoglobin O2 saturation and O2 partial pressures (PO2), measured using a CO-oximeter and a blood gas analyzer. The mixtures were kept at physiological blood pressure and temperature, constant flow, normobaric conditions, and FiO2 = 0.30. After adding PFC, the measurements suggested an increase in the transport of O2 and CO. Addition of PFC resulted in larger PO2 difference from 15 ± 2 mmHg to 23 ± 2 mmHg. Using normal blood and blood from SCD patients, the average O2 extraction ratio (O2ER) after PFC was significantly higher than baseline. Addition of saline did not cause statistically significant changes. The data suggest increased (facilitated) O2 transport by this PFC emulsion in both normal and SCD blood.

Red blood cell alloimmunization in sickle cell disease: prevalence in 2010.

BACKGROUND: Transfusion of red blood cells (RBCs) is frequently required for care of individuals with sickle cell disease (SCD). Alloimmunization rates are high and may be reduced by matching for RBC antigens that can cause alloimmunization. STUDY DESIGN AND METHODS: During the PROACTIVE Feasibility Study, patients with SCD age 2 years or older admitted for pain without acute chest syndrome were enrolled for possible randomization to preventive blood transfusion or standard care. Transfusion and antibody histories were obtained at each site, and antibody screening was done, to assess transfusion burden and alloimmunization prevalence. Participating sites were surveyed regarding antigen matching practice. RESULTS: A total of 237 patients (169 SS, 42 SC, 15 Sß(0) -thalassemia, 11 Sß(+) -thalassemia), 118 males and 119 females, were enrolled. Mean age was 19.3 years (range, 2.0-68.0); there were 122 children and 115 adults. A total of 75.8% had received at least a single transfusion of RBCs before the study. Thirty-four patients (14.4%) had a history of at least one alloantibody and 17 of these had more than one. When surveyed, 19 sites (83% of responders) reported antigen matching to at least include C, E, and K for transfusion of all patients with SCD. CONCLUSION: Though antigen typing before transfusion of people with SCD and providing antigen-negative units is now widely employed by sickle cell centers, the alloimmunization rate remains quite high in contemporary sickle cell populations and may be due in large part to transfusions received at institutions not providing extended matching.

Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE).

Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre-emptive therapy in high-risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two-thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.