How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6.

The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyl-tRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid-liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.

Graduate medical education well-being directors in the United States: who are they, and what does the role entail?

BACKGROUND: Institutional Graduate Medical Education (GME) Well-being Director (WBD) roles have recently emerged in the United States to support resident and fellow well-being. However, with a standard position description lacking, the current scope and responsibilities of such roles is unknown. This study describes the scope of work, salary support, and opportunities for role definition for those holding institutional leadership positions for GME well-being. METHODS: In November 2021, 43 members of a national network of GME WBDs in the United States were invited to complete a cross-sectional survey that included questions about job responsibilities, percent effort, and dedicated budget, and a free text response question about unique leadership challenges for GME WBDs. The survey was analyzed using descriptive statistics for quantitative data and thematic analysis for qualitative data. RESULTS: 26 members (60%) responded. Most were physicians, and the majority identified as female and White. Median percent effort salary support was 40%. A small minority reported overseeing an allocated budget. Most respondents worked to improve access to mental health services, oversaw institution-wide well-being programs, designed or delivered well-being content, provided consultations to individual programs, met with trainees, and partnered with diversity, equity, and inclusion (DEI) efforts. GME WBDs described unique challenges that had implications for perceived effectiveness related to resources, culture, institutional structure, and regulatory requirements in GME. DISCUSSION: There was high concordance for several key responsibilities, which may represent a set of core priorities for this role. Other reported responsibilities may reflect institution-specific needs or opportunities for role definition. A wide scope of responsibilities, coupled with limited defined budgetary support described by many GME Well-being Directors, could limit effective role execution. Future efforts to better define the role, optimize organizational reporting structures and provide funding commensurate with the scope of work may allow the GME Well-being Director to more effectively develop and execute strategic interventions.

Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

Current state of technical transfusion medicine practice for out-of-hospital blood transfusion in Canada.

BACKGROUND AND OBJECTIVES: Canadian out-of-hospital blood transfusion programmes (OHBTPs) are emerging, to improve outcomes of trauma patients by providing pre-hospital transfusion from the scene of injury, given prolonged transport times. Literature is lacking to guide its implementation. Thus, we sought to gather technical transfusion medicine (TM)-specific practices across Canadian OHBTPs. MATERIALS AND METHODS: A survey was sent to TM representatives of Canadian OHBTPs from November 2021 to March 2022. Data regarding transport, packaging, blood components and inventory management were included and reported descriptively. Only practices involving Blood on Board programme components for emergency use were included. RESULTS: OHBTPs focus on helicopter emergency medical service programmes, with some supplying fixed-wing aircraft and ground ambulances. All provide 1-3 coolers with 2 units of O RhD/Kell-negative red blood cells (RBCs) per cooler, with British Columbia trialling coolers with 2 units of pre-thawed group A plasma. Inventory exchanges are scheduled and blood components are returned to TM inventory using visual inspection and internal temperature data logger readings. Coolers are validated to storage durations ranging from 72 to 124 h. All programmes audit to manage wastage, though there is no consensus on appropriate benchmarks. All programmes have a process for documenting units issued, reconciliation after transfusion and for transfusion reaction reporting; however, training programmes vary. Common considerations included storage during extreme temperature environments, O-negative RBC stewardship, recipient notification, traceability, clinical practice guidelines co-reviewed by TM and a common audit framework. CONCLUSION: OHBTPs have many similarities throughout Canada, where harmonization may assist in further developing standards, leveraging best practice and national coordination.

Effects of Persistent Exposure to COVID-19 on Mental Health Outcomes Among Trainees: a Longitudinal Survey Study.

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19) has created considerable strain on the physical and mental health of healthcare workers around the world. The effects have been acute for physician trainees-a unique group functioning simultaneously as learners and care providers with limited autonomy. OBJECTIVE: To investigate the longitudinal effects of physician trainee exposure to patients being tested for COVID-19 on stress, anxiety, depression, and burnout using three surveys conducted during the early phase of the pandemic. DESIGN: Longitudinal survey study. PARTICIPANTS: All physician trainees (N = 1375) at an academic medical center. MAIN MEASURE: Assess the relationship between repeated exposure to patients being tested for COVID-19 and stress, anxiety, depression, and burnout. KEY RESULTS: Three hundred eighty-nine trainees completed the baseline survey (28.3%). Of these, 191 and 136 completed the ensuing surveys. Mean stress, anxiety, and burnout decreased by 21% (95% confidence interval (CI): - 28 to - 12%; P < 0.001), 25% (95% CI: - 36 to - 11%; P < 0.001), and 13% (95% CI: - 18 to - 7%; P < 0.001), respectively, per survey. However, for each survey time point, there was mean increase in stress, anxiety, and burnout per additional exposure: stress [24% (95% CI: + 12 to + 38%; P < 0.001)], anxiety [22% (95% CI: + 2 to + 46%; P = 0.026)], and burnout [18% (95% CI: + 10 to + 28%; P < 0.001)]. For depression, the association between exposure was strongest for the third survey, where mean depression scores increased by 33% per additional exposure (95% CI: + 18 to + 50%; P < 0.001). CONCLUSIONS: Training programs should adapt to address the detrimental effects of the "pileup" of distress associated with persistent exposure through adaptive programs that allow flexibility for time off and recovery.

Temporal Associations Between EHR-Derived Workload, Burnout, and Errors: a Prospective Cohort Study.

BACKGROUND: The temporal progression and workload-related causal contributors to physician burnout are not well-understood. OBJECTIVE: To characterize burnout's time course and evaluate the effect of time-varying workload on burnout and medical errors. DESIGN: Six-month longitudinal cohort study with measurements of burnout, workload, and wrong-patient orders every 4 weeks. PARTICIPANTS: Seventy-five intern physicians in internal medicine, pediatrics, and anesthesiology at a large academic medical center. MAIN MEASURES: Burnout was measured using the Professional Fulfillment Index survey. Workload was collected from electronic health record (EHR) audit logs and summarized as follows: total time spent on the EHR, after-hours EHR time, patient load, inbox time, chart review time, note-writing time, and number of orders. Wrong-patient orders were assessed using retract-and-reorder events. KEY RESULTS: Seventy-five of 104 interns enrolled (72.1%) in the study. A total of 337 surveys and 8,863,318 EHR-based actions were analyzed. Median burnout score across the cohort across all time points was 1.2 (IQR 0.7-1.7). Individual-level burnout was variable (median monthly change 0.3, IQR 0.1-0.6). In multivariable analysis, increased total EHR time (ß=0.121 for an increase from 54.5 h per month (25th percentile) to 123.0 h per month (75th percentile), 95%CI=0.016-0.226), increased patient load (ß=0.130 for an increase from 4.9 (25th percentile) to 7.1 (75th percentile) patients per day, 95%CI=0.053-0.207), and increased chart review time (ß=0.096 for an increase from 0.39 (25th percentile) to 0.59 (75th percentile) hours per patient per day, 95%CI=0.015-0.177) were associated with an increased burnout score. After adjusting for the total number of ordering sessions, burnout was not statistically associated with an increased rate of wrong-patient orders (rate ratio=1.20, 95%CI=0.76-1.89). CONCLUSIONS: Burnout and recovery were associated with recent clinical workload for a cohort of physician trainees, highlighting the elastic nature of burnout. Wellness interventions should focus on strategies to mitigate sustained elevations of work responsibilities.

Correction: Work-Related and Personal Factors Associated With Mental Well-Being During the COVID-19 Response: Survey of Health Care and Other Workers.

[This corrects the article DOI: 10.2196/21366.].

Risk factors associated with physician trainee concern over missed educational opportunities during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic resulted in a transformation of clinical care practices to protect both patients and providers. These changes led to a decrease in patient volume, impacting physician trainee education due to lost clinical and didactic opportunities. We measured the prevalence of trainee concern over missed educational opportunities and investigated the risk factors leading to such concerns. METHODS: All residents and fellows at a large academic medical center were invited to participate in a web-based survey in May of 2020. Participants responded to questions regarding demographic characteristics, specialty, primary assigned responsibility during the previous 2 weeks (clinical, education, or research), perceived concern over missed educational opportunities, and burnout. Multivariable logistic regression was used to assess the relationship between missed educational opportunities and the measured variables. RESULTS: 22% (301 of 1375) of the trainees completed the survey. 47% of the participants were concerned about missed educational opportunities. Trainees assigned to education at home had 2.85 [95%CI 1.33-6.45] greater odds of being concerned over missed educational opportunities as compared with trainees performing clinical work. Trainees performing research were not similarly affected [aOR = 0.96, 95%CI (0.47-1.93)]. Trainees in pathology or radiology had 2.51 [95%CI 1.16-5.68] greater odds of concern for missed educational opportunities as compared with medicine. Trainees with greater concern over missed opportunities were more likely to be experiencing burnout (p = 0.038). CONCLUSIONS: Trainees in radiology or pathology and those assigned to education at home were more likely to be concerned about their missed educational opportunities. Residency programs should consider providing trainees with research or at home clinical opportunities as an alternative to self-study should future need for reduced clinical hours arise.

Maximising and evaluating the uptake, use and impact of golf and health studies.

INTRODUCTION: The dissemination of research, and evaluation of its impact is an increasing priority for the scientific community and funders. We take the topic of golf and health and aim to outline processes that may contribute to improved research uptake, use and impact proposing a research impact (RI) tool. We then evaluate our published research using the Research Contributions Framework (RCF). METHODS: Building on existing research and frameworks we i) assessed the need for, ii) carried out and iii) published research, before iv) creating digital resources, v) sharing these resources widely and vi) evaluating our research.To evaluate uptake, use and impact of our three principal golf and health research outputs, we performed a contributions analysis, using the RCF first proposed by Morton. RESULTS/DISCUSSION: We developed a specific six-step Research Impact tool. Having implemented this, research uptake and use included over 300 press articles, a dedicated website and social media channels. Golf's global industry leadership dispersed information across >150 countries, embedded golf and health into curricula for industry professionals and used leading tournaments to promote health. National policy makers hosted dedicated meetings regarding golf and health and began to implement policy change. CONCLUSION: To date, strong uptake and use can be demonstrated for these studies, while a final contribution to impact requires further time to determine.Frameworks we used aiming to maximise impact (Research Impact tool) and evaluate its contribution to uptake, use and impact (Research Contribution Framework) could potentially add value to public health/sports medicine researchers.

Work-Related and Personal Factors Associated With Mental Well-Being During the COVID-19 Response: Survey of Health Care and Other Workers.

BACKGROUND: The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19). OBJECTIVE: The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being. METHODS: All faculty, staff, and postdoctoral fellows of a university, including its medical school, were invited in April 2020 to complete an online questionnaire measuring stress, anxiety, depression, work exhaustion, burnout, and decreased well-being. We examined associations between these outcomes and factors including work in high-risk clinical settings and family/home stressors. RESULTS: There were 5550 respondents (overall response rate of 34.3%). Overall, 34% of faculty and 14% of staff (n=915) were providing clinical care, while 61% of faculty and 77% of staff were working from home. Among all workers, anxiety (prevalence ratio 1.37, 95% CI 1.09-1.73), depression (prevalence ratio 1.28, 95% CI 1.03-1.59), and high work exhaustion (prevalence ratio 1.24, 95% CI 1.13-1.36) were independently associated with community or clinical exposure to COVID-19. Poor family-supportive behaviors by supervisors were also associated with these outcomes (prevalence ratio 1.40, 95% CI 1.21-1.62; prevalence ratio 1.69, 95% CI 1.48-1.92; and prevalence ratio 1.54, 95% CI 1.44-1.64, respectively). Age <40 years and a greater number of family/home stressors were also associated with these poorer outcomes. Among the subset of clinicians, caring for patients with COVID-19 and working in high-risk clinical settings were additional risk factors. CONCLUSIONS: Our findings suggest that the pandemic has had negative effects on the mental health and well-being of both clinical and nonclinical employees. Mitigating exposure to COVID-19 and increasing supervisor support are modifiable risk factors that may protect mental health and well-being for all workers.

Mitochondrial inefficiency in infants born to overweight African-American mothers.

BACKGROUND: Currently 20-35% of pregnant women are obese, posing a major health risk for mother and fetus. It is postulated that an abnormal maternal-fetal nutritional environment leads to adverse metabolic programming, resulting in altered substrate metabolism in the offspring and predisposing to risks of obesity and diabetes later in life. Data indicate that oocytes from overweight animals have abnormal mitochondria. We hypothesized that maternal obesity is associated with altered mitochondrial function in healthy neonatal offspring. METHODS: Overweight and obese (body mass index, (BMI) ≥ 25 kg/m2, n = 14) and lean (BMI < 25 kg/m2, n = 8), African-American pregnant women carrying male fetuses were recruited from the Barnes Jewish Hospital obstetric clinic. Maternal and infant data were extracted from medical records. Infants underwent body composition testing in the first days of life. Circumcision skin was collected for isolation of fibroblasts. Fibroblast cells were evaluated for mitochondrial function, metabolic gene expression, nutrient uptake, and oxidative stress. RESULTS: Skin fibroblasts of infants born to overweight mothers had significantly higher mitochondrial respiration without a concurrent increase in ATP production, indicating mitochondrial inefficiency. These fibroblasts had higher levels of reactive oxygen species and evidence of oxidative stress. Evaluation of gene expression in offspring fibroblasts revealed altered expression of multiple genes involved in fatty acid and glucose metabolism and mitochondrial respiration in infants of overweight mothers. CONCLUSIONS: This study demonstrates altered mitochondrial function and oxidative stress in skin fibroblasts of infants born to overweight mothers. Future studies are needed to determine the long-term impact of this finding on the metabolic health of these children.

High-sucrose-induced maternal obesity disrupts ovarian function and decreases fertility in Drosophila melanogaster.

As the obesity epidemic worsens, the prevalence of maternal obesity is expected to rise. Both high-fat and high-sucrose diets are known to promote maternal obesity and several studies have elucidated the molecular influence of high-fat feeding on female reproduction. However, to date, the molecular impact of a high-sucrose diet on maternal obesity remains to be investigated. Using our previously reported Drosophila high-sucrose maternal obesity model, we sought to determine how excess dietary sucrose impacted the ovary. High-sucrose diet (HSD) fed adult females developed systemic insulin resistance and exhibited an ovarian phenotype characterized by excess accumulation of lipids and cholesterol in the ovary, decreased ovary size, and impaired egg maturation. We also observed decreased expression of antioxidant genes and increased protein carbonylation in the ovaries of HSD females. HSD females laid fewer eggs; however, the overall survival of offspring was unchanged relative to lean control females. Ovaries of HSD females had increased mitochondrial DNA copy number and decreased expression of key mitochondrial regulators, suggestive of an ineffective compensatory response to mitochondrial dysfunction. Mitochondrial alterations were also observed in male offspring of obese females. This study demonstrates that high-sucrose-induced maternal obesity promotes insulin resistance, while disrupting ovarian metabolism and function.

Mental health care during the Ebola virus disease outbreak in Sierra Leone.

PROBLEM: Reported levels of mental health and psychosocial problems rose during the 2014-2015 Ebola virus disease outbreak in Sierra Leone. APPROACH: As part of the emergency response, existing plans to create mental health units within the existing hospital framework were brought forward. A nurse-led mental health and psychosocial support service, with an inpatient liaison service and an outpatient clinic, was set up at the largest government hospital in the country. One mental health nurse trained general nurses in psychological first aid, case identification and referral pathways. Health-care staff attended mental well-being workshops on coping with stigma and stress. LOCAL SETTING: Mental health service provision in Sierra Leone is poor, with one specialist psychiatric hospital to serve the population of 7 million. RELEVANT CHANGES: From March 2015 to February 2016, 143 patients were seen at the clinic; 20 had survived or had relatives affected by Ebola virus disease. Half the patients (71) had mild distress or depression, anxiety disorders and grief or social problems, while 30 patients presented with psychosis requiring medication. Fourteen non-specialist nurses received mental health awareness training. Over 100 physicians, nurses and auxiliary staff participated in well-being workshops. LESSONS LEARNT: A nurse-led approach within a non-specialist setting was a successful model for delivering mental health and psychosocial support services during the Ebola outbreak in Sierra Leone. Strong leadership and partnerships were essential for establishing a successful service. Lack of affordable psychotropic medications, limited human resources and weak social welfare structures remain challenges.

Two cases of the variant RHD*DAU5 allele associated with maternal alloanti-D.

CONCLUSIONS: Rh is a complex blood group system with diverse genotypes that may encode weak and partial D variants. Standard serologic analysis may identify clinically significant D variants as D+; nevertheless, individuals with these D variants should be managed as D- patients to prevent antibody formation to absent D epitopes. Variant identification is necessary during pregnancy to allow for timely and appropriate Rh immune globulin (RhIG) prophylaxis for hemolytic disease of the fetus and newborn (HDFN) as D alloimmunization can occur with some D variants. Here, we describe two cases of the RHD*DAU5 allele associated with maternal alloanti-D in patients of African ancestry. Two obstetric patients were initially serologically classified as D+ with negative antibody detection tests on routine prenatal testing. Repeat testing at delivery identified anti-D in both patients with no history of RhIG administration or transfusion. DNA sequencing revealed that both patients possessed the RHD*DAU5 allele. Cord blood testing on both infants revealed positive direct antiglobulin test (DAT) results with anti-D eluted from the red blood cells (RBCs) of one of the infants. Despite the positive DAT, neither infant experienced anemia or hyperbilirubinemia. We document two cases of pregnant women whose RBCs expressed a partial D variant and were classified as D+ on the basis of standard serologic testing, resulting in subsequent failure to provide RhIG prophylaxis. Both cases were associated with alloanti-D formation but without significant HDFN. To our knowledge, these are the first reported cases of maternal alloanti-D associated with the RHD*DAU5 partial D variant.

Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster.

The influence of nutrition on offspring metabolism has become a hot topic in recent years owing to the growing prevalence of maternal and childhood obesity. Studies in mammals have identified several factors correlating with parental and early offspring dietary influences on progeny health; however, the molecular mechanisms that underlie these factors remain undiscovered. Mammalian metabolic tissues and pathways are heavily conserved in Drosophila melanogaster, making the fly an invaluable genetic model organism for studying metabolism. In this review, we discuss the metabolic similarities between mammals and Drosophila and present evidence supporting its use as an emerging model of metabolic programming.