Expert Consensus Recommendations on the Management of Treatment-emergent Adverse Events Among Men with Prostate Cancer Taking Poly-ADP Ribose Polymerase Inhibitor + Novel Hormonal Therapy Combination Therapy.

BACKGROUND AND OBJECTIVE: Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT. METHODS: The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1-9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines. KEY FINDINGS AND LIMITATIONS: AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1-8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion. CONCLUSIONS AND CLINICAL IMPLICATIONS: This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy. PATIENT SUMMARY: A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.

Making Science Computable Using Evidence-Based Medicine on Fast Healthcare Interoperability Resources: Standards Development Project.

BACKGROUND: Evidence-based medicine (EBM) has the potential to improve health outcomes, but EBM has not been widely integrated into the systems used for research or clinical decision-making. There has not been a scalable and reusable computer-readable standard for distributing research results and synthesized evidence among creators, implementers, and the ultimate users of that evidence. Evidence that is more rapidly updated, synthesized, disseminated, and implemented would improve both the delivery of EBM and evidence-based health care policy. OBJECTIVE: This study aimed to introduce the EBM on Fast Healthcare Interoperability Resources (FHIR) project (EBMonFHIR), which is extending the methods and infrastructure of Health Level Seven (HL7) FHIR to provide an interoperability standard for the electronic exchange of health-related scientific knowledge. METHODS: As an ongoing process, the project creates and refines FHIR resources to represent evidence from clinical studies and syntheses of those studies and develops tools to assist with the creation and visualization of FHIR resources. RESULTS: The EBMonFHIR project created FHIR resources (ie, ArtifactAssessment, Citation, Evidence, EvidenceReport, and EvidenceVariable) for representing evidence. The COVID-19 Knowledge Accelerator (COKA) project, now Health Evidence Knowledge Accelerator (HEvKA), took this work further and created FHIR resources that express EvidenceReport, Citation, and ArtifactAssessment concepts. The group is (1) continually refining FHIR resources to support the representation of EBM; (2) developing controlled terminology related to EBM (ie, study design, statistic type, statistical model, and risk of bias); and (3) developing tools to facilitate the visualization and data entry of EBM information into FHIR resources, including human-readable interfaces and JSON viewers. CONCLUSIONS: EBMonFHIR resources in conjunction with other FHIR resources can support relaying EBM components in a manner that is interoperable and consumable by downstream tools and health information technology systems to support the users of evidence.

Pembrolizumab in patients with advanced upper tract urothelial carcinoma: a real-world study from ARON-2 project.

Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations.

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

Multidimensional calibration spaces in Staphylococcus Aureus detection using chitosan-based genosensors and electronic tongue.

Mastitis diagnosis can be made by detecting Staphylococcus aureus (S. aureus), which requires high sensitivity and selectivity. Here, we report on microfluidic genosensors and electronic tongues to detect S. aureus DNA using impedance spectroscopy with data analysis employing visual analytics and machine learning techniques. The genosensors were made with layer-by-layer films containing either 10 bilayers of chitosan/chondroitin sulfate or 8 bilayers of chitosan/sericin functionalized with an active layer of cpDNA S. aureus. The specific interactions leading to hybridization in these genosensors allowed for a low limit of detection of 5.90 × 10-19 mol/L. The electronic tongue had four sensing units made with 6-bilayer chitosan/chondroitin sulfate films, 10-bilayer chitosan/chondroitin sulfate, 8-bilayer chitosan/sericin, and 8-bilayer chitosan/gold nanoparticles modified with sericin. Despite the absence of specific interactions, various concentrations of DNA S. aureus could be distinguished when the impedance data were plotted using a dimensionality reduction technique. Selectivity of S. aureus DNA was confirmed using multidimensional calibration spaces, based on machine learning, with accuracy up to 89 % for the genosensors and 66 % for the electronic tongue. Hence, with these computational methods one may opt for the more expensive genosensors or the simpler and cheaper electronic tongue, depending on the sensitivity level required to diagnose mastitis.

MENDS-on-FHIR: leveraging the OMOP common data model and FHIR standards for national chronic disease surveillance.

Objectives: The Multi-State EHR-Based Network for Disease Surveillance (MENDS) is a population-based chronic disease surveillance distributed data network that uses institution-specific extraction-transformation-load (ETL) routines. MENDS-on-FHIR examined using Health Language Seven's Fast Healthcare Interoperability Resources (HL7® FHIR®) and US Core Implementation Guide (US Core IG) compliant resources derived from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to create a standards-based ETL pipeline. Materials and Methods: The input data source was a research data warehouse containing clinical and administrative data in OMOP CDM Version 5.3 format. OMOP-to-FHIR transformations, using a unique JavaScript Object Notation (JSON)-to-JSON transformation language called Whistle, created FHIR R4 V4.0.1/US Core IG V4.0.0 conformant resources that were stored in a local FHIR server. A REST-based Bulk FHIR $export request extracted FHIR resources to populate a local MENDS database. Results: Eleven OMOP tables were used to create 10 FHIR/US Core compliant resource types. A total of 1.13 trillion resources were extracted and inserted into the MENDS repository. A very low rate of non-compliant resources was observed. Discussion: OMOP-to-FHIR transformation results passed validation with less than a 1% non-compliance rate. These standards-compliant FHIR resources provided standardized data elements required by the MENDS surveillance use case. The Bulk FHIR application programming interface (API) enabled population-level data exchange using interoperable FHIR resources. The OMOP-to-FHIR transformation pipeline creates a FHIR interface for accessing OMOP data. Conclusion: MENDS-on-FHIR successfully replaced custom ETL with standards-based interoperable FHIR resources using Bulk FHIR. The OMOP-to-FHIR transformations provide an alternative mechanism for sharing OMOP data.

Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

BACKGROUND: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. METHODS: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC-transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012-2018. RESULTS: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC-transfused patients had 1 (~46%) or 2-5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte-reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. DISCUSSION: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.

Virus adsorbent systems based on Amazon holocellulose and nanomaterials.

The environment preservation has been an important motivation to find alternative, functional, and biodegradable materials to replace polluting petrochemicals. The production of nonbiodegradable face masks increased the concentration of microplastics in the environment, highlighting the need for sustainable alternatives, such as the use of local by-products to create efficient and eco-friendly filtering materials. Furthermore, the use of smart materials can reduce the risk of contagion and virus transmission, especially in the face of possible mutations. The development of novel materials is necessary to ensure less risk of contagion and virus transmission, as well as to preserve the environment. Taking these factors into account, 16 systems were developed with different combinations of precursor materials (holocellulose, polyaniline [ES-PANI], graphene oxide [GO], silver nanoparticles [AgNPs], and activated carbon [AC]). Adsorption tests of the spike protein showed that the systems containing GO and AC were the most efficient in the adsorption process. Similarly, plate tests conducted using the VSV-IN strain cultured in HepG2 cells showed that the system containing all phases showed the greatest reduction in viral titer method. In agreement, the biocompatibility tests showed that the compounds extracted from the systems showed low cytotoxicity or no significant cytotoxic effect in human fibroblasts. As a result, the adsorption tests of the spike protein, viral titration, and biocompatibility tests showed that systems labeled as I and J were the most efficient. In this context, the present research has significantly contributed to the technological development of antiviral systems, with improved properties and increased adsorption efficiency, reducing the viral titer and contributing efficiently to public health. In this way, these alternative materials could be employed in sensors and devices for filtering and sanitization, thus assisting in mitigating the transmission of viruses and bacteria. RESEARCH HIGHLIGHTS: Sixteen virus adsorbent systems were developed with different combinations of precursor materials (holocellulose, polyaniline (ES-PANI), graphene oxide (GO), silver nanoparticles (AgNPs), and activated carbon (AC)). The system that included all of the nanocomposites holocellulose, PANI, GO, AgNPs, and AC showed the greatest reduction in viral titration. The biocompatibility tests revealed that all systems caused only mild or moderate cytotoxicity toward human fibroblasts.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.

BACKGROUND: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS: Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION: This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

Management of Metastatic Urothelial Carcinoma in Emerging Markets (EM): An Expert Opinion.

Urothelial carcinoma (UC) is the 10th most common cancer globally with an almost 4 times higher prevalence in men. The main risk factors for development of urothelial carcinoma are advanced age, smoking, arsenic contamination, exposure to carcinogens. Metastatic urothelial carcinoma (mUC) has overall poor prognosis with a 5-year overall survival rate of only < 5%. The standard of care comprises of platinum-based chemotherapy, but the responses are often not sustained. A working group was established with an objective to discuss the most recent clinical data on the genitourinary tumors of interest and comprised of experts across Latin America, Emerging Asia (except China, Japan, and South Korea), Africa, and the Middle East (known as Emerging Markets or EM). There is an evident disparity in terms of uneven mortality and incidence rate distribution among various regions. There is a lack and/or insufficient data on epidemiology, treatment, and outcomes in the EM. The lack of registries impacts the healthcare decisions and the lower incidence from the region might not be reflective of the true disease burden. The treatment outcomes of mUC can be improved by understanding the current disease burden and treatment approach of mUC and identifying the gaps and challenges associated with management. Hence, a literature review was developed to summarize the current disease burden and treatment approach of mUC across EM. The review also highlights the unmet needs for mUC management in EM and suggests a way forward to improve the current situation in order to better serve the patients.

The Fit After Baby randomized controlled trial: An mHealth postpartum lifestyle intervention for women with elevated cardiometabolic risk.

BACKGROUND: Postpartum women with overweight/obesity and a history of adverse pregnancy outcomes are at elevated risk for cardiometabolic disease. Postpartum weight loss and lifestyle changes can decrease these risks, yet traditional face-to-face interventions often fail. We adapted the Diabetes Prevention Program into a theory-based mobile health (mHealth) program called Fit After Baby (FAB) and tested FAB in a randomized controlled trial. METHODS: The FAB program provided 12 weeks of daily evidence-based content, facilitated tracking of weight, diet, and activity, and included weekly coaching and gamification with points and rewards. We randomized women at 6 weeks postpartum 2:1 to FAB or to the publicly available Text4baby (T4B) app (active control). We measured weight and administered behavioral questionnaires at 6 weeks, and 6 and 12 months postpartum, and collected app user data. RESULTS: 81 eligible women participated (77% White, 2% Asian, 15% Black, with 23% Hispanic), mean baseline BMI 32±5 kg/m2 and age 31±5 years. FAB participants logged into the app a median of 51/84 (IQR 25,71) days, wore activity trackers 66/84 (IQR 43,84) days, logged weight 17 times (IQR 11,24), and did coach check-ins 5.5/12 (IQR 4,9) weeks. The COVID-19 pandemic interrupted data collection for the primary 12-month endpoint, and impacted diet, physical activity, and body weight for many participants. At 12 months postpartum women in the FAB group lost 2.8 kg [95% CI -4.2,-1.4] from baseline compared to a loss of 1.8 kg [95% CI -3.8,+0.3] in the T4B group (p = 0.42 for the difference between groups). In 60 women who reached 12 months postpartum before the onset of the COVID-19 pandemic, women randomized to FAB lost 4.3 kg [95% CI -6.0,-2.6] compared to loss in the control group of 1.3 kg [95% CI -3.7,+1.1] (p = 0.0451 for the difference between groups). CONCLUSIONS: There were no significant differences between groups for postpartum weight loss for the entire study population. Among those unaffected by the COVID pandemic, women randomized to the FAB program lost significantly more weight than those randomized to the T4B program. The mHealth FAB program demonstrated a substantial level of engagement. Given the scalability and potential public health impact of the FAB program, the efficacy for decreasing cardiometabolic risk by increasing postpartum weight loss should be tested in a larger trial.

MENDS-on-FHIR: Leveraging the OMOP common data model and FHIR standards for national chronic disease surveillance.

Objective: The Multi-State EHR-Based Network for Disease Surveillance (MENDS) is a population-based chronic disease surveillance distributed data network that uses institution-specific extraction-transformation-load (ETL) routines. MENDS-on-FHIR examined using Health Language Seven's Fast Healthcare Interoperability Resources (HL7® FHIR®) and US Core Implementation Guide (US Core IG) compliant resources derived from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to create a standards-based ETL pipeline. Materials and Methods: The input data source was a research data warehouse containing clinical and administrative data in OMOP CDM Version 5.3 format. OMOP-to-FHIR transformations, using a unique JavaScript Object Notation (JSON)-to-JSON transformation language called Whistle, created FHIR R4 V4.0.1/US Core IG V4.0.0 conformant resources that were stored in a local FHIR server. A REST-based Bulk FHIR $export request extracted FHIR resources to populate a local MENDS database. Results: Eleven OMOP tables were used to create 10 FHIR/US Core compliant resource types. A total of 1.13 trillion resources were extracted and inserted into the MENDS repository. A very low rate of non-compliant resources was observed. Discussion: OMOP-to-FHIR transformation results passed validation with less than a 1% non-compliance rate. These standards-compliant FHIR resources provided standardized data elements required by the MENDS surveillance use case. The Bulk FHIR application programming interface (API) enabled population-level data exchange using interoperable FHIR resources. The OMOP-to-FHIR transformation pipeline creates a FHIR interface for accessing OMOP data. Conclusion: MENDS-on-FHIR successfully replaced custom ETL with standards-based interoperable FHIR resources using Bulk FHIR. The OMOP-to-FHIR transformations provide an alternative mechanism for sharing OMOP data.

A Transgender Health Information Resource: Participatory Design Study.

BACKGROUND: Despite the abundance of health information on the internet for people who identify as transgender and gender diverse (TGD), much of the content used is found on social media channels, requiring individuals to vet the information for relevance and quality. OBJECTIVE: We developed a prototype transgender health information resource (TGHIR) delivered via a mobile app to provide credible health and wellness information for people who are TGD. METHODS: We partnered with the TGD community and used a participatory design approach that included focus groups and co-design sessions to identify users' needs and priorities. We used the Agile software development methodology to build the prototype. A medical librarian and physicians with expertise in transgender health curated a set of 97 information resources that constituted the foundational content of the prototype. To evaluate the prototype TGHIR app, we assessed the app with test users, using a single item from the System Usability Scale to assess feature usability, cognitive walk-throughs, and the user version of the Mobile Application Rating Scale to evaluate the app's objective and subjective quality. RESULTS: A total of 13 people who identified as TGD or TGD allies rated their satisfaction with 9 of 10 (90%) app features as good to excellent, and 1 (10%) of the features-the ability to filter to narrow TGHIR resources-was rated as okay. The overall quality score on the user version of the Mobile Application Rating Scale was 4.25 out of 5 after 4 weeks of use, indicating a good-quality mobile app. The information subscore received the highest rating, at 4.75 out of 5. CONCLUSIONS: Community partnership and participatory design were effective in the development of the TGHIR app, resulting in an information resource app with satisfactory features and overall high-quality ratings. Test users felt that the TGHIR app would be helpful for people who are TGD and their care partners.

Playing in the clinical decision support sandbox: tools and training for all.

Objectives: Introduce the CDS-Sandbox, a cloud-based virtual machine created to facilitate Clinical Decision Support (CDS) developers and implementers in the use of FHIR- and CQL-based open-source tools and technologies for building and testing CDS artifacts. Materials and Methods: The CDS-Sandbox includes components that enable workflows for authoring and testing CDS artifacts. Two workshops at the 2020 and 2021 AMIA Annual Symposia were conducted to demonstrate the use of the open-source CDS tools. Results: The CDS-Sandbox successfully integrated the use of open-source CDS tools. Both workshops were well attended. Participants demonstrated use and understanding of the workshop materials and provided positive feedback after the workshops. Discussion: The CDS-Sandbox and publicly available tutorial materials facilitated an understanding of the leading-edge open-source CDS infrastructure components. Conclusion: The CDS-Sandbox supports integrated use of the key CDS open-source tools that may be used to introduce CDS concepts and practice to the clinical informatics community.

Nanoarchitectonic E-Tongue of Electrospun Zein/Curcumin Carbon Dots for Detecting Staphylococcus aureusin Milk.

We report a nanoarchitectonic electronic tongue made with flexible electrodes coated with curcumin carbon dots and zein electrospun nanofibers, which could detect Staphylococcus aureus(S. aureus) in milk using electrical impedance spectroscopy. Electronic tongues are based on the global selectivity concept in which the electrical responses of distinct sensing units are combined to provide a unique pattern, which in this case allowed the detection of S. aureus through non-specific interactions. The electronic tongue used here comprised 3 sensors with electrodes coated with zein nanofibers, carbon dots, and carbon dots with zein nanofibers. The capacitance data obtained with the three sensors were processed with a multidimensional projection technique referred to as interactive document mapping (IDMAP) and analyzed using the machine learning-based concept of multidimensional calibration space (MCS). The concentration of S. aureus could be determined with the sensing units, especially with the one containing zein as the limit of detection was 0.83 CFU/mL (CFU stands for colony-forming unit). This high sensitivity is attributed to molecular-level interactions between the protein zein and C-H groups in S. aureus according to polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS) data. Using machine learning and IDMAP, we demonstrated the selectivity of the electronic tongue in distinguishing milk samples from mastitis-infected cows from milk collected from healthy cows, and from milk spiked with possible interferents. Calibration of the electronic tongue can also be reached with the MCS concept employing decision tree algorithms, with an 80.1% accuracy in the diagnosis of mastitis. The low-cost electronic tongue presented here may be exploited in diagnosing mastitis at early stages, with tests performed in the farms without requiring specialized laboratories or personnel.

Community Engagement in Research and Design of a Transgender Health Information Resource.

BACKGROUND: Access to credible and relevant health care information is an unmet need for the transgender and gender-diverse (TGD) community. This paper describes the community engagement methods and resulting community priorities as part of a codesign process for the development of a Transgender Health Information Resource (TGHIR) application. METHODS: A lesbian, gay, bisexual, transgender, and queer advocacy organization and an academic health sciences team partnered to establish a community advisory board (CAB) of TGD individuals, parents of TGD individuals, and clinicians with expertise in transgender health to inform the project. The analytic-deliberative model and group facilitation strategies based on Liberating Structures guided procedures. Affinity grouping was used to synthesize insights from CAB meeting notes regarding roles and perspectives on the design of the TGHIR application. We used the Patient Engagement in Research Scale (PEIRS) to evaluate CAB members' experience with the project. RESULTS: The CAB emphasized the importance of designing the application with and for the TGD community, including prioritizing intersectionality and diversity. CAB engagement processes benefited from setting clear expectations, staying focused on goals, synchronous and asynchronous work, and appreciating CAB member expertise. TGHIR application scope and priorities included a single source to access relevant, credible health information, the ability to use the app discreetly, and preserving privacy (i.e., safe use). An out-of-scope CAB need was the ability to identify both culturally and clinically competent TGD health care providers. PEIRS results showed CAB members experienced moderate to high levels of meaningful engagement (M[standard deviation] = 84.7[12] out of 100). CONCLUSION: A CAB model was useful for informing TGHIR application priority features. In-person and virtual methods were useful for engagement. The CAB continues to be engaged in application development, dissemination, and evaluation. The TGHIR application may complement, but will not replace, the need for both culturally and clinically competent health care for TGD people.

From the light blue sky to the dark deep sea: Trophic and resource partitioning between epipelagic and mesopelagic layers in a tropical oceanic ecosystem.

The connection between epipelagic and deep-sea mesopelagic realms controls a variety of ecosystem processes including oceanic carbon storage and the provision of harvestable fish stocks. So far, these two layers have been mostly addressed in isolation and the ways they connect remain poorly understood. Furthermore, both systems are affected by climate change, exploitation of resources, and increasing pervasion of pollutants. Here we use bulk isotopes of δ13C and δ15N of 60 ecosystem components to evaluate the trophic linkage between epipelagic and mesopelagic ecosystems in warm oligotrophic waters. Additionally, we we conducted a comparison of isotopic niche sizes and overlaps across multiple species to evaluate how environmental gradients between epipelagic and mesopelagic ecosystems shape ecological patterns of resource use and competition between species. Our database comprises siphonophores, crustaceans, cephalopods, salpas, fishes, and seabirds. It also includes five zooplankton size classes, two groups of fish larvae, and particulate organic matter collected at different depths. Through this wide taxonomic and trophic variety of epipelagic and mesopelagic species, we show that pelagic species access resources originating from different food sources, mostly autotrophic-based (epipelagics) and microbial heterotrophic-based (mesopelagics). This leads to a sharp trophic dissimilarity between vertical layers. Additionally, we show that trophic specialization increases in deep-sea species and argue that food availability and environmental stability are among the main drivers of this pattern. Finally, we discuss how the ecological traits of pelagic species highlighted in this study can respond to human impacts and increase their vulnerability in the Anthropocene.

The role of immune checkpoint inhibitors (ICI) as adjuvant treatment in renal cell carcinoma (RCC): A systematic review and meta-analysis.

Pembrolizumab, a PD-1 ICI is approved for the adjuvant treatment of postnephrectomy patients with clear cell RCC in some countries worldwide. However, recent negative data from randomized clinical trials (RCT) with another ICIs makes the benefit of this treatment uncertain. A systematic review and study-level meta-analysis was performed to evaluate the benefit of disease-free survival (DFS) with adjuvant ICI treatment for patients with localized and/or metastatic resected RCC. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to September 15, 2022. The statistical analysis was performed by ProMeta 3 software in intention-to-treat (ITT) population and in predetermined subgroups. Four RCT totalizing 3407 patients were included in this analysis. Systemic immunotherapy was pembrolizumab, atezolizumab, nivolumab, and ipilimumab plus nivolumab in 496, 390, 404, and 405 patients, respectively. In the ITT population there was a nonstatistically significant DFS benefit with adjuvant ICI (HR: 0.85, 95% CI: 0.69-1.04). Regarding the subgroups, there was a DFS benefit for PD-L1 positive (HR: 0.72; 95% CI: 0.55-0.94), intermediate-high risk patients (HR: 0.77; 95% CI: 0.63-0.94), and patients with sarcomatoid component (HR: 0.66; 95% CI: 0.43-0.99). This meta-analysis did not demonstrate a statistically significant DFS benefit in overall population, however considering the heterogeneity between the RCTs the use of adjuvant ICI should be individualized.

Co-design of the Transgender Health Information Resource: Web-Based Participatory Design.

BACKGROUND: There is an urgent and unmet need for accessible and credible health information within the transgender and gender-diverse (TGD) community. Currently, TGD individuals often seek and must find relevant resources by vetting social media posts. A resource that provides accessible and credible health-related resources and content via a mobile phone app may have a positive impact on and support the TGD population. OBJECTIVE: COVID-19 stay-at-home orders forced a shift in the methods used in participatory design. In this paper, we aimed to describe the web-based participatory methods used to develop the Transgender Health Information Resource. We also described and characterized the web-based engagement that occurred during a single session of the overall design process. METHODS: We planned and conducted web-based design sessions to replace the proposed in-person sessions. We used web-based collaborative tools, including Zoom (Zoom Video Communications), Mural (Mural), REDCap (Research Electronic Data Capture; Vanderbilt University), and Justinmind (Justinmind), to engage the participants in the design process. Zoom was used as an integrated platform for design activities. Mural was used to perform exercises, such as free listing, brainstorming, and grouping. REDCap allowed us to collect survey responses. Justinmind was used to create prototypes that were shared and discussed via Zoom. Recruitment was led by one of our community partners, One Colorado, who used private Facebook groups in which web-based flyers were dispersed. The design process took place in several workshops over a period of 10 months. We described and characterized engagement during a single design session by tracking the number of influential interactions among participants. We defined an influential interaction as communication, either verbal or web-based content manipulation, that advanced the design process. RESULTS: We presented data from a single design session that lasted 1 hour and 48 minutes and included 4 participants. During the session, there were 301 influential interactions, consisting of 79 verbal comments and 222 web-based content manipulations. CONCLUSIONS: Web-based participatory design can elicit input and decisions from participants to develop a health information resource, such as a mobile app user interface. Overall, participants were highly engaged. This approach maintained the benefits and fidelity of traditional in-person design sessions, mitigated deficits, and exploited the previously unconsidered benefits of web-based methods, such as enhancing the ability to participate for those who live far from academic institutions. The web-based approach to participatory design was an efficient and feasible methodological design approach.