Development of a proteomic signature associated with severe disease for patients with COVID-19 using data from 5 multicenter, randomized, controlled, and prospective studies.

Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19.

A novel, evidence-based, comprehensive clinical decision support system improves outcomes for patients with traumatic rib fractures.

BACKGROUND: Traumatic rib fractures are associated with high morbidity and mortality. Clinical decision support systems (CDSS) have been shown to improve adherence to evidence-based (EB) practice and improve clinical outcomes. The objective of this study was to investigate if a rib fracture CDSS reduced hospital length of stay (LOS), 90-day and 1-year mortality, unplanned ICU transfer, and the need for mechanical ventilation. The independent association of two process measures, an admission EB order set and a pain-inspiratory-cough score early warning system, with LOS were investigated. METHODS: The CDSS was scaled across nine US trauma centers. Following multiple imputation, multivariable regression models were fit to evaluate the association of the CDSS on primary and secondary outcomes. As a sensitivity analysis, propensity score matching was also performed to confirm regression findings. RESULTS: Overall, 3,279 patients met inclusion criteria. Rates of EB practices increased following implementation. On risk-adjusted analysis, in-hospital LOS preintervention versus postintervention was unchanged (incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 0.97-1.15, p = 0.2) but unplanned transfer to the ICU was reduced (odds ratio, 0.28; 95% CI, 0.09-0.84, p = 0.024), as was 1-year mortality (hazard ratio, 0.6; 95% CI, 0.4-0.89, p = 0.01). Provider utilization of the admission order bundle was 45.3%. Utilization was associated with significantly reduced LOS (IRR, 0.87; 95% CI, 0.77-0.98; p = 0.019). The early warning system triggered on 34.4% of patients; however, was not associated with a significant reduction in hospital LOS (IRR, 0.76; 95% CI, 0.55-1.06; p = 0.1). CONCLUSION: A novel, user-centered, comprehensive CDSS improves adherence to EB practice and is associated with a significant reduction in unplanned ICU admissions and possibly mortality, but not hospital LOS. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Re-Aiming Equity Evaluation in Clinical Decision Support: A Scoping Review of Equity Assessments in Surgical Decision Support Systems.

OBJECTIVE: We critically evaluated the surgical literature to explore the prevalence and describe how equity assessments occur when using clinical decision support systems. BACKGROUND: Clinical decision support (CDS) systems are increasingly used to facilitate surgical care delivery. Despite formal recommendations to do so, equity evaluations are not routinely performed on CDS systems and underrepresented populations are at risk of harm and further health disparities. We explored surgical literature to determine frequency and rigor of CDS equity assessments and offer recommendations to improve CDS equity by appending existing frameworks. METHODS: We performed a scoping review up to Augus 25, 2021 using PubMed and Google Scholar for the following search terms: clinical decision support, implementation, RE-AIM, Proctor, Proctor's framework, equity, trauma, surgery, surgical. We identified 1415 citations and 229 abstracts met criteria for review. A total of 84 underwent full review after 145 were excluded if they did not assess outcomes of an electronic CDS tool or have a surgical use case. RESULTS: Only 6% (5/84) of surgical CDS systems reported equity analyses, suggesting that current methods for optimizing equity in surgical CDS are inadequate. We propose revising the RE-AIM framework to include an Equity element (RE 2 -AIM) specifying that CDS foundational analyses and algorithms are performed or trained on balanced datasets with sociodemographic characteristics that accurately represent the CDS target population and are assessed by sensitivity analyses focused on vulnerable subpopulations. CONCLUSION: Current surgical CDS literature reports little with respect to equity. Revising the RE-AIM framework to include an Equity element (RE 2 -AIM) promotes the development and implementation of CDS systems that, at minimum, do not worsen healthcare disparities and possibly improve their generalizability.

Evaluation of federated learning variations for COVID-19 diagnosis using chest radiographs from 42 US and European hospitals.

OBJECTIVE: Federated learning (FL) allows multiple distributed data holders to collaboratively learn a shared model without data sharing. However, individual health system data are heterogeneous. "Personalized" FL variations have been developed to counter data heterogeneity, but few have been evaluated using real-world healthcare data. The purpose of this study is to investigate the performance of a single-site versus a 3-client federated model using a previously described Coronavirus Disease 19 (COVID-19) diagnostic model. Additionally, to investigate the effect of system heterogeneity, we evaluate the performance of 4 FL variations. MATERIALS AND METHODS: We leverage a FL healthcare collaborative including data from 5 international healthcare systems (US and Europe) encompassing 42 hospitals. We implemented a COVID-19 computer vision diagnosis system using the Federated Averaging (FedAvg) algorithm implemented on Clara Train SDK 4.0. To study the effect of data heterogeneity, training data was pooled from 3 systems locally and federation was simulated. We compared a centralized/pooled model, versus FedAvg, and 3 personalized FL variations (FedProx, FedBN, and FedAMP). RESULTS: We observed comparable model performance with respect to internal validation (local model: AUROC 0.94 vs FedAvg: 0.95, P = .5) and improved model generalizability with the FedAvg model (P < .05). When investigating the effects of model heterogeneity, we observed poor performance with FedAvg on internal validation as compared to personalized FL algorithms. FedAvg did have improved generalizability compared to personalized FL algorithms. On average, FedBN had the best rank performance on internal and external validation. CONCLUSION: FedAvg can significantly improve the generalization of the model compared to other personalization FL algorithms; however, at the cost of poor internal validity. Personalized FL may offer an opportunity to develop both internal and externally validated algorithms.

Combined Expert and User-Driven Usability Assessment of Trauma Decision Support Systems Improves User-Centered Design.

BACKGROUND: Trauma clinical decision support systems improve adherence with evidence-based practice but suffer from poor usability and the lack of a user-centered design. The objective of this study was to compare the effectiveness of user and expert-driven usability testing methods to detect usability issues in a rib fracture clinical decision support system and identify guiding principles for trauma clinical decision support systems. METHODS: A user-driven and expert-driven usability investigation was conducted using a clinical decision support system developed for patients with rib fractures. The user-driven usability evaluation was as follows: 10 clinicians were selected for simulation-based usability testing using snowball sampling, and each clinician completed 3 simulations using a video-conferencing platform. End-users participated in a novel team-based approach that simulated realistic clinical workflows. The expert-driven heuristic evaluation was as follows: 2 usability experts conducted a heuristic evaluation of the clinical decision support system using 10 common usability heuristics. Usability issues were identified, cataloged, and ranked for severity using a 4-level ordinal scale. Thematic analysis was utilized to categorize the identified usability issues. RESULTS: Seventy-nine usability issues were identified; 63% were identified by experts and 48% by end-users. Notably, 58% of severe usability issues were identified by experts alone. Only 11% of issues were identified by both methods. Five themes were identified that could guide the design of clinical decision support systems-transparency, functionality and integration into workflow, automated and noninterruptive, flexibility, and layout and appearance. Themes were preferentially identified by different methods. CONCLUSION: We found that a dual-method usability evaluation involving usability experts and end-users drastically improved detection of usability issues over single-method alone. We identified 5 themes to guide trauma clinical decision support system design. Performing usability testing via a remote video-conferencing platform facilitated multi-site involvement despite a global pandemic.

Surgical management of delayed-presentation diaphragm hernia: A single-institution experience.

Objectives: Delayed-presentation diaphragm hernias are uncommon, and surgical management varies widely across practices. We describe our surgical experience with delayed-presentation diaphragm hernias as a case series of 14 patients, 9 of whom underwent minimally invasive repair. Methods: We performed a retrospective chart review of our prospective database of all patients treated surgically for delayed-presentation diaphragm hernia at our institution from January 1, 2005, to April 30, 2021. We excluded patients with poststernotomy, post-left ventricular assist device, and previously diagnosed congenital hernias. We recorded patient demographics, etiology, laterality, chronicity, operative details, postoperative complications, and long-term results. Results: We performed surgical repair of delayed-presentation diaphragm hernia in 14 patients. Eleven patients (79%) were male, the median age was 61 (18-83) years, the median body mass index was 29.2 (14.5-33.7), and 8 (57%) hernias were left-sided. Etiology was trauma (n = 7, 50%), iatrogenic (n = 5, 36%), and unknown (n = 2, 14%). Median time to presentation in patients with traumatic and iatrogenic hernias was 7.5 years (6 weeks to 38 years). Nine patients (64%) underwent minimally invasive repair, and 5 patients (36%) underwent open repair. We used a synthetic patch in all but 2 patients (86%). Median length of stay was 5 (3-27) days. Two patients (14%) had major complications. There were no deaths. Twelve patients (86%) had follow-up imaging at a median follow-up of 17 months (1-192) with zero recurrences. Conclusions: Our experience suggests that a minimally invasive or an open approach to patients with a delayed-presentation diaphragm hernia is safe and effective. We recommend tailoring the surgical approach based on patient characteristics, anatomic considerations, and surgeons' experience.

Barriers to and Facilitators for Acceptance of Comprehensive Clinical Decision Support System-Driven Care Maps for Patients With Thoracic Trauma: Interview Study Among Health Care Providers and Nurses.

BACKGROUND: Comprehensive clinical decision support (CDS) care maps can improve the delivery of care and clinical outcomes. However, they are frequently plagued by usability problems and poor user acceptance. OBJECTIVE: This study aims to characterize factors influencing successful design and use of comprehensive CDS care maps and identify themes associated with end-user acceptance of a thoracic trauma CDS care map earlier in the process than has traditionally been done. This was a planned adaptive redesign stage of a User Acceptance and System Adaptation Design development and implementation strategy for a CDS care map. This stage was based on a previously developed prototype CDS care map guided by the Unified Theory of Acceptance and Use of Technology. METHODS: A total of 22 multidisciplinary end users (physicians, advanced practice providers, and nurses) were identified and recruited using snowball sampling. Qualitative interviews were conducted, audio-recorded, and transcribed verbatim. Generation of prespecified codes and the interview guide was informed by the Unified Theory of Acceptance and Use of Technology constructs and investigative team experience. Interviews were blinded and double-coded. Thematic analysis of interview scripts was conducted and yielded descriptive themes about factors influencing the construction and potential use of an acceptable CDS care map. RESULTS: A total of eight dominant themes were identified: alert fatigue (theme 1), automation (theme 2), redundancy (theme 3), minimalistic design (theme 4), evidence based (theme 5), prevent errors (theme 6), comprehensive across the spectrum of disease (theme 7), and malleability (theme 8). Themes 1 to 4 addressed factors directly affecting end users, and themes 5 to 8 addressed factors affecting patient outcomes. More experienced providers prioritized a system that is easy to use. Nurses prioritized a system that incorporated evidence into decision support. Clinicians across specialties, roles, and ages agreed that the amount of extra work generated should be minimal and that the system should help them administer optimal care efficiently. CONCLUSIONS: End user feedback reinforces attention toward factors that improve the acceptance and use of a CDS care map for patients with thoracic trauma. Common themes focused on system complexity, the ability of the system to fit different populations and settings, and optimal care provision. Identifying these factors early in the development and implementation process may facilitate user-centered design and improve adoption.

Palatal Injection for the Removal of Maxillary Teeth: Current Practice Among Oral and Maxillofacial Surgeons.

PURPOSE: Conventional teaching regarding palatal injection for the removal of maxillary teeth dictates the administration of buccal and palatal injections. Recently, some investigators have questioned the necessity of the palatal injection, suggesting that contemporary local anesthetics might diffuse sufficiently across the buccopalatal cortical bone distance. It has been suggested that because the buccopalatal cortical bone distance increases anteriorly to posteriorly in the maxilla, the success of maxillary extractions with buccal injection only might be related to the anteroposterior position of the tooth. Evidence from clinical trials has only recently become available. Since 2006, 15 clinical trials that examined outcomes of maxillary tooth extractions performed with buccal injection of local anesthetic only have been published. However, there are limited data available on the clinical practice of surgeons. MATERIALS AND METHODS: An online survey was sent to 276 full members of the Canadian Association of Oral and Maxillofacial Surgeons. Respondents were asked about their use of palatal injection for the removal of maxillary teeth under local anesthesia, including how often they administer a palatal injection for maxillary extractions in each region of the maxilla. RESULTS: Ninety-two responses were received (33%). Most practitioners deliver a palatal injection for every maxillary tooth extraction under local anesthesia. However, there is a substantial number who do not always administer a palatal injection (ie, they give it "most of the time," "occasionally," or "never"). This number decreased in a linear fashion anteriorly to posteriorly in the maxilla (incisors, 17 of 89; canines, 16 of 88; premolars, 13 of 88; first and second molars, 10 of 89; third molars, 10 of 88). CONCLUSION: Some surgeons who do not always administer a palatal injection for extraction of maxillary teeth under local anesthesia. The number is larger for anterior compared with posterior teeth.

Exploring Australian Aboriginal women's experiences of menopause: a descriptive study.

BACKGROUND: Despite extensive literature demonstrating differing experiences in menopause around the world, documentation of the experience of menopause in Australian Aboriginal women is scarce, and thus their menopausal experience is relatively unknown. This study aimed to understand Australian Aboriginal women's understanding and experience of menopause and its impact on their lives. METHODS: The study was an exploratory qualitative study. Twenty-five Aboriginal women were recruited from a regional centre in the Mid-West region of Western Australia using opportunistic and snowballing sampling. Interviews and focus group discussions were undertaken from February 2011 to February 2012 using open-ended questioning with a yarning technique. Thematic analysis was undertaken of the transcribed interviews. RESULTS: A number of themes were revealed. These related to the language used, meanings and attitudes to menopause, symptoms experienced, the role of men, a lack of understanding, coping mechanisms and the attribution of menopausal changes to something else. The term "change of life" was more widely recognised and signified the process of ageing, and an associated gain of respect in the local community. A fear of menopausal symptoms or uncertainty about their origin was also common. Overall, many women reported insufficient understanding and a lack of available information to assist them and their family to understand the transition. CONCLUSION: There are similarities between Aboriginal and non-Aboriginal experiences of menopause, including similar symptom profiles. The current language used within mainstream health settings may not be appropriate to this population if it fails to recognise the importance of language and reflect the attributed meaning of menopause. The fear of symptoms and uncertainty of their relationship to menopause demonstrated a need for more information which has not adequately been supplied to Australian Aboriginal women through current services. While this study is with a select population of Aboriginal Australian women, it reveals the importance of acknowledging differences, particularly in use of language to convey ideas and support Aboriginal women experiencing menopause.

Menopause and the influence of culture: another gap for Indigenous Australian women?

BACKGROUND: There is great variation in experience of menopause in women around the world. The purpose of this study was to review current understanding of Australian Aboriginal and Torres Strait Islander (Indigenous) women's experiences of menopause. The literature pertaining to the perception, significance and experience of menopause from a number of cultural groups around the world has been included to provide context for why Indigenous women's experience might be important for their health and differ from that reported in other studies of Australian women and menopause. METHODS: A search of databases including Ovid Medline, Pubmed, Web of Science, AUSThealth, AMED, EMBASE, Global Health and PsychINFO was undertaken from January 2011 to April 2011 using the search terms menopause, Indigenous, Aboriginal, attitudes, and perceptions and repeated in September 2012. RESULTS: Considerable research shows significant variation across cultures in the menopausal experience. Biological, psychological, social and cultural factors are associated with either positive or negative attitudes, perceptions or experiences of menopause in various cultures. Comparative international literature shows that neither biological nor social factors alone are sufficient to explain the variation in experiences of the menopausal transition. However, a strong influence of culture on the menopause experience can be found. The variation in women's experience of menopause indicates that different cultural groups of women may have different understandings and needs during the menopausal transition. While considerable literature exists for Australian women as a whole, there has been little investigation of Australian Indigenous women, with only two research studies related to Indigenous women's experiences of menopause identified. CONCLUSIONS: Differences in biocultural experience of menopause around the world suggest the importance of biocultural research. For the Indigenous women of Australia, the relative contribution of culture, social disadvantage and poor general health compared with non-Indigenous women to the experience of menopause is unknown. As such, further research and understanding of the experience of Indigenous women around Australia is needed. This information could assist individuals, families, cultural groups and healthcare providers to enhance management and support for Indigenous Australian women.

Acute ingestion of different macronutrients differentially enhances aspects of memory and attention in healthy young adults.

The role of carbohydrates on mood and cognition is fairly well established, however research examining the behavioural effects of the other macronutrients is limited. The current study compared the effects of a 25 g glucose drink to energetically matched protein and fat drinks and an inert placebo. Following a blind, placebo-controlled, randomised crossover design, 18 healthy young adults consumed drinks containing fat, glucose, protein and placebo. Cognitive performance was examined at baseline and again 15- and 60 min post drink. Mood was assessed at baseline and then 10-, 35- and 80 min post drink. Attention and speed were enhanced 15 min following fat or glucose ingestion and working memory was enhanced 15 min following protein ingestion. Sixty minutes post drink memory enhancements were observed after protein and memory impairment was observed following glucose. All drinks increased ratings of alertness. The findings suggest that macronutrients: (i) have different windows of opportunity for effects (ii) target different cognitive domains.

Vitamins and psychological functioning: a mobile phone assessment of the effects of a B vitamin complex, vitamin C and minerals on cognitive performance and subjective mood and energy.

OBJECTIVES: Despite being widely consumed, the effects of multi-vitamin supplements on psychological functioning have received little research attention. METHODS: Using a mobile phone testing paradigm, 198 males (30-55 years) in full-time employment took part in this randomised, placebo-controlled, double-blind, parallel-groups trial assessing the effects of a multi-vitamin/mineral on cognitive performance and psychological state/mood. Participants completed two cognitive tasks and a number of visual analogue scales (VAS) before and after a full day's work, on the day before, and 7, 14, 21 and 28 days after, commencing their treatment. RESULTS: Participants in the vitamin/mineral group rated themselves as having greater 'physical stamina' across assessments and weeks. They also rated themselves as having had greater 'concentration' and 'mental stamina' during the working day at the assessment carried out after a day's work, but not at the time of the assessment completed prior to work. Participants in this group also reported greater subjective 'alertness' on Bond-Lader mood scales during the post-work assessment on day 14 and both the pre and post-work assessments on day 28. CONCLUSIONS: These findings complement the results from the laboratory-based, randomised-controlled trial in the same cohort and suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation.