An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Quantitative bias analysis for external control arms using real-world data in clinical trials: a primer for clinical researchers.

Development of medicines in rare oncologic patient populations are growing, but well-powered randomized controlled trials are typically extremely challenging or unethical to conduct in such settings. External control arms using real-world data are increasingly used to supplement clinical trial evidence where no or little control arm data exists. The construction of an external control arm should always aim to match the population, treatment settings and outcome measurements of the corresponding treatment arm. Yet, external real-world data is typically fraught with limitations including missing data, measurement error and the potential for unmeasured confounding given a nonrandomized comparison. Quantitative bias analysis (QBA) comprises a collection of approaches for modelling the magnitude of systematic errors in data which cannot be addressed with conventional statistical adjustment. Their applications can range from simple deterministic equations to complex hierarchical models. QBA applied to external control arm represent an opportunity for evaluating the validity of the corresponding comparative efficacy estimates. We provide a brief overview of available QBA approaches and explore their application in practice. Using a motivating example of a comparison between pralsetinib single-arm trial data versus pembrolizumab alone or combined with chemotherapy real-world data for RET fusion-positive advanced non-small cell lung cancer (aNSCLC) patients (1-2% among all NSCLC), we illustrate how QBA can be applied to external control arms. We illustrate how QBA is used to ascertain robustness of results despite a large proportion of missing data on baseline ECOG performance status and suspicion of unknown confounding. The robustness of findings is illustrated by showing that no meaningful change to the comparative effect was observed across several 'tipping-point' scenario analyses, and by showing that suspicion of unknown confounding was ruled out by use of E-values. Full R code is also provided.

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy.

INTRODUCTION: Olanzapine use for chemotherapy-induced nausea and vomiting (CINV) in hematological malignancies, for multi-day chemotherapy, and with a steroid-sparing antiemetic strategy is poorly understood. This study investigated if olanzapine is associated with improved prevention of CINV when added to a steroid-sparing antiemetic regimen in patients with acute leukemia receiving intensive, moderately emetogenic, multi-day chemotherapy. METHODS: This was a single-center, retrospective cohort study in patients with acute leukemia. Patients who received olanzapine for CINV prevention were compared to those who did not. All patients received a 5-HT3 antagonist. Adult patients receiving moderately emetogenic, multi-day, intensive chemotherapy for acute leukemia were included. Patients were excluded if they received steroids greater than physiological doses during the study period. The primary endpoint was the complete response of CINV (no emesis or rescue antiemetic usage). RESULTS: This study included 58 patients, 12 patients received olanzapine and 46 patients were in the control group. Baseline demographics were similar. In the study population, 89.7% had acute myeloid leukemia, median age was 54 (interquartile range 42-63) years, 34.5% were female, 27.6% had prior CINV. Complete response of CINV was similar between groups, 4 (33.3%) and 15 (32.6%) patients in the olanzapine and control groups, respectively. Safety events were similar between groups. CONCLUSION: Patients with acute leukemia receiving multi-day intensive chemotherapy are at high risk for CINV. The limited data in this study suggests that olanzapine use within a steroid-sparing antiemetic regimen was well tolerated and associated with similar incidence and severity of CINV compared to the control group.

Predicting Progression of Oral Lesions to Malignancy Using Machine Learning.

OBJECTIVE: To use large-scale electronic health record (EHR) data to develop machine learning models predicting malignant transformation of oral lesions. METHODS: A multi-institutional health system database was used to identify a retrospective cohort of patients with biopsied oral lesions. The primary outcome was malignant transformation. Chart review and automated system database queries were used to identify a range of demographic, clinical, and pathologic variables. Machine learning was used to develop predictive models for progression to malignancy. RESULTS: There were 2192 patients with a biopsied oral lesion, of whom 1232 had biopsy proven oral dysplasia. There was malignant transformation in 34% of patients in the oral lesions dataset, and in 54% of patients in the dysplasia subset. Multiple machine learning-based models were trained on the data in two experiments, (a) including all patients with biopsied oral lesions and (b) including only patients with biopsy-proven dysplasia. In the first experiment, the best machine learning models predicted malignant transformation among the biopsied oral lesions with an area under the curve (AUC) of 86%. In the second experiment, the random forest model predicted malignant transformation among lesions with dysplasia with an AUC of 0.75. The most influential features were dysplasia grade and the presence of multiple lesions, with smaller influences from other features including anemia, histopathologic description of atypia, and other prior cancer history. CONCLUSION: With diverse features from EHR data, machine learning approaches are feasible and allow for generation of models that predict which oral lesions are likely to progress to malignancy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1156-1162, 2023.

Transportability of Overall Survival Estimates From US to Canadian Patients With Advanced Non-Small Cell Lung Cancer With Implications for Regulatory and Health Technology Assessment.

Importance: The external validity of survival outcomes derived from clinical practice data from US patients with advanced non-small cell lung cancer (NSCLC) is not known and is of potential importance because it may be used to support regulatory decision-making and health technology assessment outside of the US. Objective: To evaluate whether overall survival (OS) estimates for a selected group of patients with advanced NSCLC from a large US clinical practice database are transportable to Canadian patients receiving the same systemic therapies. Design, Setting, and Participants: This retrospective multicenter cohort study used transportability analysis to assess whether adjustment for pretreatment characteristics of eligible patient cohorts could reliably approximate OS estimated from US-based samples to Canadian populations. A total of 17 432 eligible adult patients who were diagnosed de novo with advanced NSCLC on or after January 1, 2011, were included in the analysis and followed up until September 30, 2020. Because data on race and ethnicity were available in the US database but not the Canadian database and because racial and ethnic distribution was likely to be similar between US and Canadian patients, these characteristics were not analyzed. Exposures: Initiation of platinum-doublet chemotherapy or pembrolizumab monotherapy as first-line systemic treatment for advanced NSCLC. Main Outcomes and Measures: OS measured from the time of initiation of the respective treatment regimen. Results: Among 17 432 eligible patients, 15 669 patients from the US and 1763 patients from Canada were included in the analysis. Of those, 11 863 patients (sample size-weighted estimates of mean [SD] age, 68.0 [9.3] years; 6606 [55.7%] male; 10 100 from the US and 1763 from Canada) were included in the subset of patients with complete data for baseline covariates. A total of 13 532 US patients received first-line chemotherapy, and 2137 received first-line pembrolizumab monotherapy. Of those, 8447 patients (62.4%) in the first-line chemotherapy group and 1653 patients (77.3%) in the first-line pembrolizumab group had complete data on baseline covariates for outcome model estimation. A total of 1476 Canadian patients who received first-line chemotherapy and 287 patients who received first-line pembrolizumab monotherapy were identified from the target population. After standardization to baseline patient covariates in the Canadian cohorts, transported OS estimates revealed a less than 5% mean absolute difference from the observed OS in the target population (0.56% over 60 months of follow-up in the first-line chemotherapy group and 4.54% over 30 months of follow-up in the first-line pembrolizumab group). Negative control analysis using a mismatched outcome model revealed a 6.64% discrepancy and an incompatible survival curve shape. The results were robust to assumptions of random missingness for baseline covariates, to unadjusted differences in baseline metastases and comorbidities, and to differences in the standard of care between the US and Canada related to administration of second-line anti-programmed cell death 1 ligand 1 immunotherapy for patients who initiated first-line chemotherapy. Conclusions and Relevance: The results of this cohort study suggest that, under specific circumstances, OS estimates from US clinical practice data can be adjusted using baseline clinical characteristics to closely approximate OS in selected groups of Canadian patients with advanced NSCLC. These results may have implications for regulatory decision-making and health technology assessment in target populations outside of the US.

Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer.

As advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature.

Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

Importance: There is a need to tailor treatments to patients who are most likely to derive the greatest benefit from them to improve patient outcomes and enhance cost-effectiveness of cancer therapies. Objective: To compare overall survival (OS) between patients with a current or former history of smoking with patients who never smoked and initiated pembrolizumab monotherapy as first-line (1L) treatment for advanced non-small lung cancer (NSCLC). Design, Setting, and Participants: This retrospective cohort study compared patients diagnosed with advanced NSCLC aged 18 or higher selected from a nationwide real-world database originating from more than 280 US cancer clinics. The study inclusion period was from January 1, 2011, to October 1, 2019. Exposures: Smoking status at the time of NSCLC diagnosis. Main Outcomes and Measures: OS measured from initiation of 1L pembrolizumab monotherapy. Results: In this retrospective cohort study, a total of 1166 patients (median [IQR] age, 72.9 [15.3] years; 581 [49.8%] men and 585 [50.2%] women) were assessed in the primary analysis, including 91 patients [7.8%] with no history of smoking (ie, never-smokers) and 1075 patients [92.2%] who currently or formerly smoked (ie, ever-smokers). Compared with ever-smokers, never-smokers were older (median age [IQR] of 78.2 [12.0] vs 72.7 [15.5] years), more likely to be female (61 [67.0%] vs 524 [48.7%]) and to have been diagnosed with nonsquamous tumor histology (70 [76.9%] vs 738 [68.7%]). After adjustment for baseline covariates, ever-smokers who initiated 1L pembrolizumab had significantly prolonged OS compared to never-smokers (median OS: 12.8 [10.9-14.6] vs 6.5 [3.3-13.8] months; hazard ratio (HR): 0.69 [95% CI, 0.50-0.95]). This trend was observed across all sensitivity analyses for the 1L pembrolizumab cohort, but not for initiators of 1L platinum chemotherapy, for which ever-smokers showed significantly shorter OS compared with never-smokers (HR, 1.2 [95% CI, 1.07-1.33]). Conclusions and Relevance: In patients with advanced NSCLC who received 1L pembrolizumab monotherapy in routine clinical practices in the US, patients who reported a current or former history of smoking at the time of diagnosis had consistently longer OS than never-smokers. This finding suggests that in never-smoking advanced NSCLC, 1L pembrolizumab monotherapy may not be the optimal therapy selection, and genomic testing for potential genomically matched therapies should be prioritized over pembrolizumab in never-smokers.

Thromboelastography Changes of Whole Blood Compared to Blood Component Transfusion in Infant Craniosynostosis Surgery.

ABSTRACT: Surgical treatment of craniosynostosis with cranial vault reconstruction in infants is associated with significant blood loss. The optimal blood management approach is an area of active investigation. Thromboelastography (TEG) was used to examine changes in coagulation after surgical blood loss that was managed by transfusion with either whole blood or blood components. Transfusion type was determined by availability of whole blood from the blood bank.This retrospective study examined differences in posttransfusion TEG maximum amplitude (MA), a measure of the maximum clot strength, for patients transfused with whole blood or blood components. We included all patients less than 24 months old who underwent cranial vault remodeling, received intraoperative transfusions with whole blood or blood components, and had baseline and posttransfusion TEG measured. Whole blood was requested for all patients and was preferentially used when it was available from the American Red Cross.Of 48 eligible patients, 30 received whole blood and 18 received blood components. All patients received an intraoperative antifibrinolytic agent. The posttransfusion MA in the whole blood group was 61.8 mm (IQR 59.1, 64.1) compared to 57.9 mm (IQR 50.5, 60.9) in the blood components group (P = 0.010). There was a greater posttransfusion decrease in MA for patients transfused with blood components (median decrease of 7.7 mm [IQR -3.4, 6.3]) compared with whole blood (median decrease of 2.1 mm [IQR -9.6, 7.5] P < 0.001).Transfusion with blood components was associated with a greater decrease in MA that was likely related to decreased postoperative fibrinogen in this group. Patients who received whole blood had higher postoperative fibrinogen levels.

Keeping it real: implications of real-world treatment outcomes for first-line immunotherapy in metastatic non-small-cell lung cancer.

Tweetable abstract Recent RWD studies suggest that the performance of immunotherapy in NSCLC is not as good as that seen in RCTs. However, analyses using RWD (and their interpretation) require careful appraisal and quantification of possible sources of bias.

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation.

INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Pediatric airway management.

PURPOSE OF REVIEW: Children are at risk of severe hypoxemia in the perioperative period owing to their unique anatomy and physiology. Safe and effective airway management strategies are therefore key to the practice of pediatric anesthesia. The goal of this review is to highlight recent publications (2019-2021) aimed to advance pediatric airway safety and to highlight a proposed simple, pediatric-specific, universal framework to guide clinical practice. RECENT FINDINGS: Recent investigations demonstrate that infants with normal and difficult airways experience high incidences of multiple laryngoscopy attempts and resulting hypoxemia. Video laryngoscopy may improve tracheal intubation first attempt success rate in infants with normal airways. In infants with difficult airways, standard blade video laryngoscopy is associated with higher first attempt success rates over non-standard blade video laryngoscopy. Recent studies in children with Pierre Robin sequence and mucopolysaccharidoses help guide airway equipment and technique selection. Department airway leads and hospital difficult airway services are necessary to disseminate knowledge, lead quality improvement initiatives, and promote evidence-based practice guidelines. SUMMARY: Pediatric airway management morbidity is a common problem in pediatric anesthesia. Improvements in individual practitioner preparation and management strategies as well as systems-based policies are required. A simple, pediatric-specific, universal airway management framework can be adopted for safe pediatric anesthesia practice.

Independent risk factors associated with higher mortality rates and recurrence of brain abscesses from head and neck sources.

OBJECTIVE: The aim of this study was to identify the features and independent risk factors associated with recurrence and mortality in patients with brain abscesses of head and neck origin. STUDY DESIGN: We designed a retrospective study of patients diagnosed with a brain abscess at the Massachusetts General Hospital between 1980 and 2017. Inclusion criteria were complete medical records, including medical and surgical history; and radiographic and microbiologic data. Multinomial logistic regression and Gray's test were used to evaluate the independent variables associated with recurrence and mortality. RESULTS: Eighty-eight cases met the inclusion criteria. Of these, 48 patients (54.5%) were men (mean age 50.5 ± 18.8 years). Significant association between etiology and cultured organisms was found only in cases of neurosurgical intervention with staphylococcal or streptococcal isolates (P < .05). Seizure activity was the only significant predictor of recurrence. Predictors of mortality included advanced age (P = .005); staphylococcal infection (P = .029); low monocyte count (P = .004); hyponatremia (P = .002); elevated blood urea nitrogen (P = .000); elevated creatinine (P = .002); hyperglycemia (P = .023); and status at discharge (P = .000). CONCLUSIONS: Independent risk factors, such as low monocyte count, hyponatremia, renal dysfunction, and hyperglycemia, were found to be associated with higher mortality rates in patients with brain abscesses of head and neck origin. These abnormalities should be promptly recognized and aggressively treated.

Do brain abscesses have a higher incidence of odontogenic origin than previously thought?

OBJECTIVE: The aim of this study was to answer the following clinical question: "In patients admitted to a tertiary care hospital with a diagnosis of brain abscess, how common is odontogenic etiology?" STUDY DESIGN: We designed a retrospective study of patients with brain abscesses diagnosed at the Massachusetts General Hospital between 1980 and 2017. Inclusion criteria were complete medical records outlining clinical course, relevant dental history, and radiographic and microbiologic data. RESULTS: Of 167 intracranial abscesses, 88 (52.7%) originated from a head/neck source, and 12 (13.6%) were of odontogenic etiology. Dental radiographs in 7 cases showed active dental infection. The remaining 5 patients reported recent dental procedures. Frontal lobe localization was the most common (7 of 12 [58.3%]). Presenting signs included headache (66.7%), mental status changes (41.6%), visual deficits (41.6%), and speech difficulties (33.3%). Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed all diagnoses. Drainage via open craniotomy was performed in 6 (50%) of 12 patients, and stereotactic CT-guided drainage in 4 (33.3%). The most common pathogens were Streptococcus milleri (45.5%), Staphylococcus species (27.3%), and Fusobacterium (27.3%). All cases had favorable outcomes. Five had residual neurologic deficits, 4 had persistent visual complaints, and a recurrent abscess developed in 1 case. CONCLUSIONS: These findings showed a higher subset (13.6%) of brain abscesses that could be attributed to odontogenic etiology than previously reported in the literature and highlight the need to rule out dental sources in cryptogenic cases.

Non-neural surface ectodermal rosette formation and F-actin dynamics drive mammalian neural tube closure.

The mechanisms underlying mammalian neural tube closure remain poorly understood. We report a unique cellular process involving multicellular rosette formation, convergent cellular protrusions, and F-actin cable network of the non-neural surface ectodermal cells encircling the closure site of the posterior neuropore, which are demonstrated by scanning electron microscopy and genetic fate mapping analyses during mouse spinal neurulation. These unique cellular structures are severely disrupted in the surface ectodermal transcription factor Grhl3 mutants that exhibit fully penetrant spina bifida. We propose a novel model of mammalian neural tube closure driven by surface ectodermal dynamics, which is computationally visualized.

An overview of precision oncology basket and umbrella trials for clinicians.

With advancements in biomarkers and momentum in precision medicine, biomarker-guided trials such as basket trials and umbrella trials have been developed under the master protocol framework. A master protocol refers to a single, overarching design developed to evaluate multiple hypotheses with the general goal of improving the efficiency of trial evaluation. One type of master protocol is the basket trial, in which a targeted therapy is evaluated for multiple diseases that share common molecular alterations or risk factors that may help predict whether the patients will respond to the given therapy. Another variant of a master protocol is the umbrella trial, in which multiple targeted therapies are evaluated for a single disease that is stratified into multiple subgroups based on different molecular or other predictive risk factors. Both designs follow the core principle of precision medicine-to tailor intervention strategies based on the patient's risk factor(s) that can help predict whether they will respond to a specific treatment. There have been increasing numbers of basket and umbrella trials, but they are still poorly understood. This article reviews common characteristics of basket and umbrella trials, key trials and recent US Food and Drug Administration approvals for precision oncology, and important considerations for clinical readers when critically evaluating future publications on basket trials and umbrella trials and for researchers when designing these clinical trials.

Minimizing control group allocation in randomized trials using dynamic borrowing of external control data - An application to second line therapy for non-small cell lung cancer.

BACKGROUND: Enrollment of participants to control arms in clinical trials can be challenging. This is particularly an issue in oncology trials where the standard-of-care is shifting rapidly and several promising experimental treatments are undergoing phase III testing. Novel methods for utilizing external control data may mitigate these challenges, but applied examples are sparse. Here, we therefore illustrate how Bayesian dynamic borrowing of external individual patient level control data from similar clinical trials can often reduce randomization to the control intervention without substantially trading-off precision. We further explore which types of scenarios yield viable trade-offs, and which do not. PATIENTS AND METHODS: We obtained individual patient data on patients being treated with second-line therapy for non-small cell lung cancer from Project Data Sphere with minimal in/exclusion criteria restrictions, and applied Bayesian hierarchical models with uninformative priors to generate illustrative synthetic control groups. RESULTS: Four phase III clinical trials were identified and utilized in our analysis. Even when studies which are knowingly incongruent with one another are selected to generate a synthetic control, the nature of this methodology minimizes improper borrowing from historical data. The use of a small concurrent control group within a trial greatly reduces penalized selection, and our results demonstrate the ability to reduce allocation to the control group by up to 80% with a minimal increase in uncertainty when closely matched historical data is available. CONCLUSION: Dynamic borrowing using Bayesian hierarchical models with uninformative priors represents a novel approach to utilizing external controls for comparative estimates using single arm evidence.

Patient-centered design in developing a mobile application for oral anticancer medications.

OBJECTIVES: To develop and test the usability and feasibility of a customizable mobile application (app) designed to help educate patients about their oral anticancer medications (OAMs) and regimens. SETTING: Outpatient cancer center and oncology pharmacy for urban, Midwestern academic health system. PRACTICE DESCRIPTION: Clinically-supervised educational intervention to support patients learning about OAMs. PRACTICE INNOVATION: With input from patient partners, our interdisciplinary team designed the first known tablet-based educational app that can interface with a patient's electronic medical record. The app is based on learning style and adherence theories and is customizable for individually prescribed OAMs. The app can accommodate multiple learning styles through text at 6th-grade reading level, pictures, animations, and audio voiceovers. Functionalities include interactive educational modules on 11 OAMs and case-based patient stories on common barriers to OAM adherence. EVALUATION: Early phase testing provided the opportunity to observe the user interface with the app and app functionality. Data were summarized descriptively from observations and comments of patient subjects. RESULTS: Thirty patient subjects provided input-19 in phase 1 usability testing and 11 in phase 2 feasibility testing. Comments provided by patient subjects during usability testing were largely positive. Responses included self-identification with patient stories, usefulness of drug information, preferences for text messages, and app limitations (e.g., perceived generational digital divide in technology use and potential patient inability to receive text messages). Using their feedback, modifications were made to the prototype app. Responses in feasibility testing demonstrated the app's usefulness across a wide range of ages. Highest opinion ratings on app usefulness were stated by patients who were newer to OAM therapy. CONCLUSION: User feedback suggests the potential benefit of the app as a tool to help patients with cancer, particularly after the first months for those starting new OAM regimens. Processes and lessons learned are transferable to other settings.

Care Standardization Reduces Blood Donor Exposures and Transfusion in Complex Cranial Vault Reconstruction.

BACKGROUND: Complex cranial vault reconstruction (CCVR) often requires a large-volume transfusion of blood products. We implemented a series of improvement interventions to reduce blood donor exposures (BDE) and transfusion requirements in CCVR. METHODS: We implemented interventions over 4 epochs: (E1) reconstituted blood (1:1 ratio of donor-matched red blood cells and fresh-frozen plasma) for intraoperative transfusions, (E2) reconstituted blood plus postoperative transfusion guidelines, (E3) reconstituted blood plus intraoperative antifibrinolytics and postoperative guidelines, and (E4) fresh whole blood for intraoperative transfusion, antifibrinolytics, and postoperative guidelines. Primary outcomes, BDE, and total volume of blood products transfused are presented by using statistical process control charts, with statistical comparisons between each epoch and baseline data. RESULTS: We included 347 patients <72 months old who underwent CCVR between 2008 and 2016 (E1: n = 50; E2: n = 41; E3: n = 87; and E4: n = 169). They were compared with a baseline sample group of 138 patients who were managed between 2001 and 2006. Compared with our baseline group, patients in each epoch had a significant reduction in BDE (P = .02-<.0001). Conversely, compared with the baseline group, we observed an increase the volume of blood products transfused in E1 (P = .004), no difference in E2 (P = .6) or E3 (P = .46), and a reduction in the volume of blood products transfused in E4 (P < .0001). CONCLUSIONS: The implementation of sequential clinical improvement strategies resulted in a sustained reduction in BDE whereas only the use of whole blood resulted in a significant reduction in the total volume of blood products transfused in children undergoing CCVR.

Design of Customized Mobile Application for Patient Adherence to Oral Anticancer Medications Utilizing User-Centered Design.

Adherence and compliance to oral anticancer medications (OAMs) can be challenging for patients due to their complex regimens. The goal of this research project was to design an effective and engaging user interface (UI), based on user-centered design (UCD) and incorporate animations, to reinforce and improve patient's understanding of the key aspects of taking OAMs. This current paper encompasses the development process and describes the initial phase of the project, which focused on the design and development of the tablet-based educational application (app). A UCD approach was implemented by consulting with oncology clinicians and patients at an early stage of development. Animations were developed and incorporated to convey complex medical concepts and information. An iterative design process will help ensure that the tool is customized for patient engagement.