The association of out-of-hospital postpartum NSAID use and post-discharge hypertension control for people with hypertensive disorders of pregnancy.

OBJECTIVE: To evaluate the relationship between amount of NSAID use postpartum and outpatient blood pressure (BP) control. STUDY DESIGN: This is a prospective, single-site, cohort study of postpartum people diagnosed with HDP from 2018 to 2020 using the American College of Obstetrician and Gynecologists criteria. All participants were provided an electronic BP cuff for daily evaluation after discharge. Those who provided at least 7 days of data within the first 14 days after discharge were included. Standard PP pain management included ibuprofen 600 mg every 6 h as needed. The exposure was self-reported amount of NSAIDs used within the first 14 days after discharge. The primary outcome was median mean arterial pressure (MAP) over the first 14 days after hospital discharge. Secondary outcomes included median and maximum systolic and diastolic BPs and need for PP readmission for HDP. Regression models were created, controlling for a propensity score for highest quartile of NSAID use. RESULTS: 103 participants were approached, of whom 60 met inclusion criteria. Those who had a history of a cesarean delivery were more likely to be in the highest quartile of NSAID use; no other significant differences were noted across quartiles of NSAID use. There was no association between NSAID amount used and median MAP (adjusted ß coefficient 0.03, 95% CI: -0.17 to 0.22). There were no significant associations between NSAID amount used and all other secondary outcomes. CONCLUSION: Out-of-hospital NSAID use is not associated with worsened PP BP control after hospital discharge among people diagnosed with HDP.

Barriers to medication adherence in sickle cell disease: A comprehensive theory-based evaluation using the COM-B model.

BACKGROUND: Sickle cell disease (SCD) affects more than 100,000 Americans, with complications such as pain episodes and acute chest syndrome. Despite the efficacy of hydroxyurea in reducing these complications, adherence remains low. Study objectives were to examine barriers to hydroxyurea adherence, and to evaluate the relationship between barriers and their impact on adherence. METHODS: In this cross-sectional study, patients with SCD and their caregivers were enrolled if they were taking hydroxyurea. Study measures included demographics, self-report of adherence using visual analog scale (VAS), and the Disease Management and Barriers Interview (DMI)-SCD. The DMI-SCD was mapped to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. RESULTS: Forty-eight caregivers (females 83%, median age 38 [34-43]) and 19 patients (male 53%, median age 15 [13.5-18]) participated. Using VAS, many patients (63%) reported low hydroxyurea adherence, while most caregivers (75%) reported high adherence. Caregivers endorsed barriers across multiple COM-B components, with physical opportunity (e.g., cost) and reflective motivation (e.g., SCD perceptions) being the most identified categories (48% and 42%), respectively. Patients' most identified barriers included psychological capability (e.g., forgetfulness) and reflective motivation (84% and 68%), respectively. Patients' and caregivers' VAS scores negatively correlated with the number of barriers (rs  = -.53, p = .01; rs  = -.28, p = .05) and COM-B categories (rs  = -.51, p = .02; rs  = -.35, p = .01), respectively, suggesting lower adherence with more endorsed barriers. CONCLUSIONS: Fewer barriers to hydroxyurea adherence were associated with higher adherence. Understanding barriers to adherence is essential to develop tailored interventions aimed at improving adherence.

Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents.

BACKGROUND: Sickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low. OBJECTIVE: To assess the relationship of HU adherence to health care utilization and patients' characteristics. METHODS: This is a 5-year retrospective chart review. Patients' demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin "HbF%", mean corpuscular volume "MCV", and absolute neutrophil count "ANC". Age groups included children (<12 years), adolescents (12-17 years), and young adults (≥18 years). RESULTS: A total of 113 SCD patients on HU were included (median age 14 years, IQR 10-20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p = .003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p = .01) and lower ANC (103/ml) (3.25 vs. 4.9 vs. 4.2, p = .01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p = .04; ANC 3.6 vs. 6.3, p = .002; MCV 102.3 vs. 93.1, p = .1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (rs=-0.26, p = .01; rs=-0.23, p = .01; rs=0.24, p = .01) and hospitalizations (rs=-0.27, p = .01; rs=-0.31, p = .01; rs=0.21, p = .02) as well as shorter length of stays (rs=-0.27, p = .0045; rs=-.34, p = 0.004; rs=0.23, p = .02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients' sex, socio-economic status, distance from hospital, and HU duration. CONCLUSIONS: Young adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.KEY MESSAGESYoung adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.No significant association of HU adherence to patients' sex, socio-economic status and distance from hospital.

Evaluating the transcriptional fidelity of cancer models.

BACKGROUND: Cancer researchers use cell lines, patient-derived xenografts, engineered mice, and tumoroids as models to investigate tumor biology and to identify therapies. The generalizability and power of a model derive from the fidelity with which it represents the tumor type under investigation; however, the extent to which this is true is often unclear. The preponderance of models and the ability to readily generate new ones has created a demand for tools that can measure the extent and ways in which cancer models resemble or diverge from native tumors. METHODS: We developed a machine learning-based computational tool, CancerCellNet, that measures the similarity of cancer models to 22 naturally occurring tumor types and 36 subtypes, in a platform and species agnostic manner. We applied this tool to 657 cancer cell lines, 415 patient-derived xenografts, 26 distinct genetically engineered mouse models, and 131 tumoroids. We validated CancerCellNet by application to independent data, and we tested several predictions with immunofluorescence. RESULTS: We have documented the cancer models with the greatest transcriptional fidelity to natural tumors, we have identified cancers underserved by adequate models, and we have found models with annotations that do not match their classification. By comparing models across modalities, we report that, on average, genetically engineered mice and tumoroids have higher transcriptional fidelity than patient-derived xenografts and cell lines in four out of five tumor types. However, several patient-derived xenografts and tumoroids have classification scores that are on par with native tumors, highlighting both their potential as faithful model classes and their heterogeneity. CONCLUSIONS: CancerCellNet enables the rapid assessment of transcriptional fidelity of tumor models. We have made CancerCellNet available as a freely downloadable R package ( https://github.com/pcahan1/cancerCellNet ) and as a web application ( http://www.cahanlab.org/resources/cancerCellNet_web ) that can be applied to new cancer models that allows for direct comparison to the cancer models evaluated here.

Access to Technology and Preferences for an mHealth Intervention to Promote Medication Adherence in Pediatric Acute Lymphoblastic Leukemia: Approach Leveraging Behavior Change Techniques.

BACKGROUND: Suboptimal adherence to 6-mercaptopurine (6-MP) is prevalent in pediatric acute lymphoblastic leukemia (ALL) and associated with increased risk of relapse. Rapid uptake of personal technology makes mobile health (mHealth) an attractive platform to promote adherence. OBJECTIVE: Study objectives were to examine access to mobile technology and preferences for an mHealth intervention to improve medication adherence in pediatric ALL. METHODS: A cross-sectional survey was administered in oncology clinic to parents of children with ALL as well as adolescents and young adults (AYAs) with ALL receiving maintenance chemotherapy. RESULTS: A total of 49 parents (median age [IQR] 39 [33-42] years; female 76% [37/49]) and 15 patients (median age [IQR] 17 [16-19]; male 80% [12/15]) participated. All parents and AYAs owned electronic tablets, smartphones, or both. Parents' most endorsed mHealth app features included a list of medications (71%, 35/49), information about 6-MP (71%, 35/49), refill reminders (71%, 35/49), and reminders to take 6-MP (71%, 35/49). AYAs' most endorsed features included refill reminders (73%, 11/15), reminders to take 6-MP (73%, 11/15), and tracking 6-MP (73%, 11/15). CONCLUSIONS: Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL.

Applying the COM-B model to patient-reported barriers to medication adherence in pediatric acute lymphoblastic leukemia.

BACKGROUND: Adherence to oral chemotherapy, including 6-mercaptopurine (6-MP), is suboptimal in pediatric acute lymphoblastic leukemia (ALL), which is associated with increased risk of relapse. Study objectives were to examine self-reported adherence to 6-MP and related barriers to adherence, mapped to the capability, opportunity, motivation, and behavior (COM-B) model for behavior change. PROCEDURE: Forty-nine parents (median, 39 years old; 76% females) and 15 patients (median, 17 years old, 20% females) completed the study survey. RESULTS: Suboptimal adherence was reported in 43% of parents and 73% of patients. Most parents and patients (80% and 90%, respectively) reported ≥1 adherence barrier. Parents reported difficulty helping their child meet others with ALL (43%), contacting community organizations (39%), and meeting other parents (37%). Patients reported difficulty finding out what their medications are (40%), finding out what 6-MP does (47%), and meeting other patients (40%). Using the COM-B, we found that parents and patients endorsed barriers in multiple components, especially physical (55%, 67%) and social opportunity (56%, 47%), highlighting that barriers to adherence may be multifaceted. CONCLUSIONS: Our results suggest that parents and patients with ALL face various prevalent barriers to medication adherence and provide insight into the development of behavioral interventions focused on promoting adherence, which is essential to prevent relapse and optimize health outcomes in ALL.

The Las Vegas mass shooting: An analysis of blood component administration and blood bank donations.

BACKGROUND: The deadliest mass shooting in modern United States history occurred on October 1, 2017, in Las Vegas, killing 58 and overwhelming hospitals with more than 600 injured. The scope of the tragedy offers insight into medical demands, which may help guide preparedness for future mass shooting incidents. METHODS: Retrospective, deidentified, health care institution-provided data from all hospitals and blood banks providing care to Las Vegas shooting victims were gathered. Study authors independently reviewed all data and cross-referenced it for verification. Main outcomes and measures include the number of victims requiring hospital and intensive care admission, the amount and types of blood components transfused during the first 24 hours, and the amount of blood donated to local blood banks following the Las Vegas mass shooting. RESULTS: Two hundred twenty patients required hospital admission, 68 of them to critical care. Nearly 500 blood components were transfused during the first 24 hours in a red blood cell-to-plasma-to-platelet ratio of 1:0.54:0.81. Public citizens donated almost 800 units of blood immediately after the shooting; greater than 17% of this donated blood went unused. CONCLUSIONS: The amount of blood components transfused per patient admitted was similar in magnitude to other mass casualty events, and available blood supply met patient demand. The public call for blood donors was not necessary to meet immediate demand and led to resource waste. Preparation for future mass shooting incidents should include training the community in hemorrhage control, encouraging routine blood donation, and avoiding public calls for blood donation unless approved by local blood suppliers. LEVEL OF EVIDENCE: Therapeutic study, level V.

Comparison of Tri-folded and Scroll-based Graft Viability in Preloaded Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To compare corneal endothelial damage associated with 2 techniques for preloaded Descemet membrane endothelial keratoplasty (DMEK): a tri-folded graft stored in a plastic cartridge designed for DMEK and a scrolled graft stored in a modified Jones Tube, at the time of preparation and after shipping. METHODS: DMEK grafts were prepared at the Rocky Mountain Lions Eye Bank. The grafts were either tri-folded and loaded in a plastic cartridge or scrolled and loaded into a modified Jones Tube. In each group, the grafts were then either immediately removed from the cartridges or shipped for 48 hours. The grafts were then stained with Calcein AM and imaged using a fluorescent microscope. Endothelial cell loss (ECL) was determined using trainable segmentation in Fiji by 2 graders. At each time point, rates of ECL loss were compared across the 2 groups. To explore the role of donor characteristics, a multivariable regression model was produced to account for method (tri-folding vs. scroll), donor age, donor gender, death-to-preservation time, death-to-preparation time, and shipping. RESULTS: A total of 40 grafts were prepared, processed, imaged, and analyzed. No significant difference in cell loss was seen between groups at either time point alone. In the multivariate model, no significant increase in cell loss was associated with either tri-folding (3.7% less ECL; P = 0.051) or shipping (4.3% less ECL; P = 0.049). CONCLUSIONS: All techniques used resulted in clinically acceptable levels of ECL. Tri-folded tissue in a plastic cartridge did not result in ECL inferior to a scroll when prepared either immediately or preloaded for 48 hours.

Viability of Descemet Membrane Endothelial Keratoplasty Grafts Folded in the Eye Bank.

PURPOSE: Preloaded, trifolded grafts in Descemet membrane endothelial keratoplasty require transfer of the trifolding process from the corneal transplant surgeon to the eye bank technician. We sought to assess whether trifolding may be safely conducted by an eye bank technician with cell loss comparable to standard peeling and lifting. METHODS: A total of 10 grafts were stained, peeled, and transferred directly onto a bed of Calcein-AM and Amvisc Plus by an eye bank technician. Five grafts were removed and stained as a scroll, and 5 grafts were trifolded with the endothelium in before transfer. Photographs were acquired with an inverted fluorescence microscope, and image segmentation was performed. A t test was conducted to compare differences in endothelial cell loss across groups. RESULTS: Mean cell loss in the scroll group was 18.5% [95% confidence interval (CI): 15.2%-21.9%] compared with 7.6% of the trifolded group (95% CI: 1.7%-13.5%). A 2-tailed t test indicated decreased cell loss in the trifolded group (P = 0.013). CONCLUSIONS: Despite additional manipulation of the graft, trifolding of Descemet membrane and endothelium may be performed by an eye bank technician without significantly increased cell loss relative to graft preparation as a scroll.

Association between Participants' Characteristics, Patient-Reported Outcomes, and Clinical Outcomes in Youth with Sickle Cell Disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic debilitating illness. SCD-related complications result in substantial impairment in quality of life (QOL). Our study objective was to assess the relationship of participants' characteristics, QOL, hydroxyurea adherence, and SCD-related clinical outcomes in youth with SCD. PROCEDURE: A single-center cross-sectional study. Thirty-four youth with SCD enrolled from clinic between January and December 2015. Participants completed PROMIS® measures and ©Modified Morisky Adherence Scale. RESULTS: Participants had a mean age of 14.8 (SD 2.9) years and 41% were female. Participants' age correlated with fatigue (rs=0.48; P=0.006), pain (rs=0.32; P=0.07), and anxiety (rs=0.33; P=0.06) scores. Participants with chronic pain had worse upper extremity physical function (P=0.05), pain (P=0.04), anxiety (P=0.05), and depression (P=0.05). Males reported significantly higher hydroxyurea adherence (5.4 versus 3.6, P=0.02) compared to females. Participants with chronic pain had more frequent hospitalizations (P=0.02), emergency room visits (P=0.04), and longer total length of hospital stays over 12-month period (P=0.01). CONCLUSIONS: Older and female participants had worse QOL scores, and males reported higher hydroxyurea adherence. Participants with chronic pain reported significant impairment in different QOL domains and had increased healthcare utilization. Future longitudinal studies examining the relationship between participants' characteristics, QOL, hydroxyurea adherence, and SCD-related clinical outcomes are needed.