Barriers, Solutions, and Opportunities for Adapting Critical Care Clinical Trials in the COVID-19 Pandemic.

Importance: The COVID-19 pandemic created unprecedented challenges for clinical trials worldwide, threatening premature closure and trial integrity. Every phase of research operations was affected, often requiring modifications to protocol design and implementation. Objectives: To identify the barriers, solutions, and opportunities associated with continuing critical care trials that were interrupted during the pandemic, and to generate suggestions for future trials. Design, Setting, and Participants: This mixed-methods study performed an explanatory sequential analysis involving a self-administered electronic survey and focus groups of principal investigators (PIs) and project coordinators (PCs) conducting adult and pediatric individual-patient randomized trials of the Canadian Critical Care Trials Group during the COVID-19 pandemic. Eligible trials were actively enrolling patients on March 11, 2020. Data were analyzed between September 2023 and January 2024. Main Outcomes and Measures: Importance ratings of barriers to trial conduct and completion, solutions employed, opportunities arising, and suggested strategies for future trials. Quantitative data examining barriers were analyzed using descriptive statistics. Data addressing solutions, opportunities, and suggestions were analyzed by qualitative content analysis. Integration involved triangulation of data sources and perspectives about 13 trials, synthesized by an interprofessional team incorporating reflexivity and member-checking. Results: A total of 13 trials run by 29 PIs and PCs (100% participation rate) were included. The highest-rated barriers (on a 5-point scale) to ongoing conduct during the pandemic were decisions to pause all clinical research (mean [SD] score, 4.7 [0.8]), focus on COVID-19 studies (mean [SD] score, 4.6 [0.8]), and restricted family presence in hospitals (mean [SD] score, 4.1 [0.8]). Suggestions to enable trial progress and completion included providing scientific leadership, implementing technology for communication and data management, facilitating the informed consent process, adapting the protocol as necessary, fostering site engagement, initiating new sites, streamlining ethics and contract review, and designing nested studies. The pandemic necessitated new funding opportunities to sustain trial enrollment. It increased public awareness of critical illness and the importance of randomized trial evidence. Conclusions and Relevance: While underscoring the vital role of research in society and drawing the scientific community together with a common purpose, the pandemic signaled the need for innovation to ensure the rigor and completion of ongoing trials. Lessons learned to optimize research procedures will help to ensure a vibrant clinical trials enterprise in the future.

The kinase Rio1 and a ribosome collision-dependent decay pathway survey the integrity of 18S rRNA cleavage.

The 18S rRNA sequence is highly conserved, particularly at its 3'-end, which is formed by the endonuclease Nob1. How Nob1 identifies its target sequence is not known, and in vitro experiments have shown Nob1 to be error-prone. Moreover, the sequence around the 3'-end is degenerate with similar sites nearby. Here, we used yeast genetics, biochemistry, and next-generation sequencing to investigate a role for the ATPase Rio1 in monitoring the accuracy of the 18S rRNA 3'-end. We demonstrate that Nob1 can miscleave its rRNA substrate and that miscleaved rRNA accumulates upon bypassing the Rio1-mediated quality control (QC) step, but not in healthy cells with intact QC mechanisms. Mechanistically, we show that Rio1 binding to miscleaved rRNA is weaker than its binding to accurately processed 18S rRNA. Accordingly, excess Rio1 results in accumulation of miscleaved rRNA. Ribosomes containing miscleaved rRNA can translate, albeit more slowly, thereby inviting collisions with trailing ribosomes. These collisions result in degradation of the defective ribosomes utilizing parts of the machinery for mRNA QC. Altogether, the data support a model in which Rio1 inspects the 3'-end of the nascent 18S rRNA to prevent miscleaved 18S rRNA-containing ribosomes from erroneously engaging in translation, where they induce ribosome collisions. The data also demonstrate how ribosome collisions purify cells of altered ribosomes with different functionalities, with important implications for the concept of ribosome heterogeneity.

Secondary Surgery Following Lapidus Bunionectomy.

While the Lapidus bunionectomy is a common procedure utilized to address hallux valgus, the incidence of secondary surgery is not well established. Our primary goal was to determine the incidence of revision surgery and hardware removal following the Lapidus bunionectomy in addition to the risk factors associated with each. A retrospective nested case-control study of adult patients who underwent a Lapidus bunionectomy for symptomatic hallux valgus over a nine-year period was performed. The incidence rates and 95% confidence intervals (CI) of secondary surgery in the three years following the procedure along with the estimated independent associations and odds ratios between baseline demographic, clinical, and radiographic characteristics were calculated. Of the original cohort of 2,540 patients, 127 were identified (5.0%; CI: 4.1%, 5.8%) who underwent revision surgery and 165 (6.5%; CI: 5.5%, 7.5%) who underwent hardware removal following Lapidus bunionectomy. Initially, the hallux valgus angle, intermetatarsal angle, and tibial sesamoid position were risk factors for revision surgery. However, in adjusted analyses for revision surgery, using a screw for third point of fixation emerged as the only independent risk factor (odds ratio [OR]=3.01; CI: 1.59, 5.69). In adjusted analyses for hardware removal, female sex (OR=2.33; CI: 1.08, 5.00) and third point of fixation (OR=2.92; CI: 1.82, 4.69) emerged as independent risk factors. While the overall risks associated with Lapidus bunionectomy are low and the need for revision surgery are low, this study helps to identify specific risk factors for secondary surgery and hardware removal to help in evaluation and discussion with patients. LEVEL OF EVIDENCE: : 4.

Enabling Health Information Recommendation Using Crowdsourced Refinement in Web-Based Health Information Applications: User-Centered Design Approach and EndoZone Informatics Case Study.

BACKGROUND: In the digital age, search engines and social media platforms are primary sources for health information, yet their commercial interests-focused algorithms often prioritize irrelevant content. Web-based health applications by reputable sources offer a solution to circumvent these biased algorithms. Despite this advantage, there remains a significant gap in research on the effective integration of content-ranking algorithms within these specialized health applications to ensure the delivery of personalized and relevant health information. OBJECTIVE: This study introduces a generic methodology designed to facilitate the development and implementation of health information recommendation features within web-based health applications. METHODS: We detail our proposed methodology, covering conceptual foundation and practical considerations through the stages of design, development, operation, review, and optimization in the software development life cycle. Using a case study, we demonstrate the practical application of the proposed methodology through the implementation of recommendation functionalities in the EndoZone platform, a platform dedicated to providing targeted health information on endometriosis. RESULTS: Application of the proposed methodology in the EndoZone platform led to the creation of a tailored health information recommendation system known as EndoZone Informatics. Feedback from EndoZone stakeholders as well as insights from the implementation process validate the methodology's utility in enabling advanced recommendation features in health information applications. Preliminary assessments indicate that the system successfully delivers personalized content, adeptly incorporates user feedback, and exhibits considerable flexibility in adjusting its recommendation logic. While certain project-specific design flaws were not caught in the initial stages, these issues were subsequently identified and rectified in the review and optimization stages. CONCLUSIONS: We propose a generic methodology to guide the design and implementation of health information recommendation functionality within web-based health information applications. By harnessing user characteristics and feedback for content ranking, this methodology enables the creation of personalized recommendations that align with individual user needs within trusted health applications. The successful application of our methodology in the development of EndoZone Informatics marks a significant progress toward personalized health information delivery at scale, tailored to the specific needs of users.

Food Insecurity and Hypoglycemia among Older Patients with Type 2 Diabetes Treated with Insulin or Sulfonylureas: The Diabetes & Aging Study.

BACKGROUND: Severe hypoglycemia is a serious adverse drug event associated with hypoglycemia-prone medications; older patients with diabetes are particularly at high risk. Economic food insecurity (food insecurity due to financial limitations) is a known risk factor for hypoglycemia; however, less is known about physical food insecurity (due to difficulty cooking or shopping for food), which may increase with age, and its association with hypoglycemia. OBJECTIVE: Study associations between food insecurity and severe hypoglycemia. DESIGN: Survey based cross-sectional study. PARTICIPANTS: Survey responses were collected in 2019 from 1,164 older (≥ 65 years) patients with type 2 diabetes treated with insulin or sulfonylureas. MAIN MEASURES: Risk ratios (RR) for economic and physical food insecurity associated with self-reported severe hypoglycemia (low blood glucose requiring assistance) adjusted for age, financial strain, HbA1c, Charlson comorbidity score and frailty. Self-reported reasons for hypoglycemia endorsed by respondents. KEY RESULTS: Food insecurity was reported by 12.3% of the respondents; of whom 38.4% reported economic food insecurity only, 21.1% physical food insecurity only and 40.5% both. Economic food insecurity and physical food insecurity were strongly associated with severe hypoglycemia (RR = 4.3; p = 0.02 and RR = 4.4; p = 0.002, respectively). Missed meals ("skipped meals, not eating enough or waiting too long to eat") was the dominant reason (77.5%) given for hypoglycemia. CONCLUSIONS: Hypoglycemia prevention efforts among older patients with diabetes using hypoglycemia-prone medications should address food insecurity. Standard food insecurity questions, which are used to identify economic food insecurity, will fail to identify patients who have physical food insecurity only.

Willingness to take less medication for type 2 diabetes among older patients: The Diabetes & Aging Study.

BACKGROUND: To examine the willingness of older patients to take less diabetes medication (de-intensify) and to identify characteristics associated with willingness to de-intensify treatment. METHODS: Survey conducted in 2019 in an age-stratified, random sample of older (65-100 years) adults with diabetes on glucose-lowering medications in the Kaiser Permanente Northern California Diabetes Registry. We classified survey responses to the question: "I would be willing to take less medication for my diabetes" as willing, neutral, or unwilling to de-intensify. Willingness to de-intensify treatment was examined by several clinical characteristics, including American Diabetes Association (ADA) health status categories used for individualizing glycemic targets. Analyses were weighted to account for over-sampling of older individuals. RESULTS: A total of 1337 older adults on glucose-lowering medication(s) were included (age 74.2 ± 6.0 years, 44% female, 54.4% non-Hispanic white). The proportions of participants willing, neutral, or unwilling to take less medication were 51.2%, 27.3%, and 21.5%, respectively. Proportions of willing to take less medication varied by age (65-74 years: 54.2% vs. 85+ years: 38.5%) and duration of diabetes (0-4 years: 61.0% vs. 15+ years: 44.2%), both p < 0.001. Patients on 1-2 medications were more willing to take less medication(s) compared with patients on 10+ medications (62.1% vs. 46.6%, p = 0.03). Similar proportions of willingness to take less medications were seen across ADA health status, and HbA1c. Willingness to take less medication(s) was similar across survey responses to questions about patient-clinician relationships. CONCLUSIONS: Clinical guidelines suggest considering treatment de-intensification in older patients with longer duration of diabetes, yet patients with these characteristics are less likely to be willing to take less medication(s).

Does epidemiological evidence support the success story of Uganda's response to COVID-19?

Uganda has received praise for its success in dealing with the COVID-19 pandemic. This opinion piece uses publically available data from Johns Hopkins University to suggest that it is far from clear whether the Public Health and Social Measures (PHSM) introduced in Uganda influenced the course of the first outbreak. In addition, the analysis of data from the second and third waves in Uganda suggest that government action had little or no effect on these outbreaks. The dominant narrative of successful PHSM, therefore, needs to be reconsidered, and alternative explanations for the low rates of COVID-19-related mortality in the country need to be further understood.

Emergency research without prior consent in the United States, Canada, European Union and United Kingdom: How regulatory differences affect study design and implementation in cardiac arrest trials.

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research. Data sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK). Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data. Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design.

High-Quality eHealth Websites for Information on Endometriosis: Systematic Search.

BACKGROUND: eHealth websites are increasingly being used by community members to obtain information about endometriosis. Additionally, clinicians can use these websites to enhance their understanding of the condition and refer patients to these websites. However, poor-quality information can adversely impact users. Therefore, a critical evaluation is needed to assess and recommend high-quality endometriosis websites. OBJECTIVE: This study aimed to evaluate the quality and provide recommendations for high-quality endometriosis eHealth websites for the community and clinicians. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines informed 2 Google searches of international and Australian eHealth websites. The first search string used the terms "endometriosis," "adenomyosis," or "pelvic pain," whereas "Australia" was added to the second search string. Only free eHealth websites in English were included. ENLIGHT, a validated tool, was used to assess the quality across 7 domains such as usability, visual design, user engagement, content, therapeutic persuasiveness, therapeutic alliance, and general subjective evaluation. Websites with a total score of 3.5 or more were classified as "good" according to the ENLIGHT scoring system and are recommended as high-quality eHealth websites for information on endometriosis. RESULTS: In total, 117 eHealth websites were screened, and 80 were included in the quality assessment. Four high-quality eHealth websites (ie, those that scored 3.5 or more) were identified (Endometriosis Australia Facebook Page, Endometriosis UK, National Action Plan for Endometriosis on EndoActive, and Adenomyosis by the Medical Republic). These websites provided easily understood, engaging, and accurate information. Adenomyosis by the Medical Republic can be used as a resource in clinical practice. Most eHealth websites scored well, 3.5 or more in the domains of usability (n=76, 95%), visual design (n=64, 80%), and content (n=63, 79%). However, of the 63 websites, only 25 provided references and 26 provided authorship details. Few eHealth websites scored well on user engagement (n=18, 23%), therapeutic persuasiveness (n=2, 3%), and therapeutic alliance (n=22, 28%). In total, 30 (38%) eHealth websites scored well on general subjective evaluation. CONCLUSIONS: Although geographical location can influence the search results, we identified 4 high-quality endometriosis eHealth websites that can be recommended to the endometriosis community and clinicians. To improve quality, eHealth websites must provide evidence-based information with appropriate referencing and authorship. Factors that enhance usability, visual design, user engagement, therapeutic persuasiveness, and therapeutic alliance can lead to the successful and long-term uptake of eHealth websites. User engagement, therapeutic persuasiveness, and therapeutic alliance can be strengthened by sharing lived experiences and personal stories and by cocreating meaningful content for both the community and clinicians. Reach and discoverability can be improved by leveraging search engine optimization tools. TRIAL REGISTRATION: PROSPERO CRD42020185475; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185475&VersionID=2124365.

Continuous Glucose Monitor Metrics Are Associated with Emergency Department Visits and Hospitalizations for Hypoglycemia and Hyperglycemia, but Have Low Predictive Value.

Objective: Determine whether continuous glucose monitor (CGM) metrics can provide actionable advance warning of an emergency department (ED) visit or hospitalization for hypoglycemic or hyperglycemic (dysglycemic) events. Research Design and Methods: Two nested case-control studies were conducted among insulin-treated diabetes patients at Kaiser Permanente, who shared their CGM data with their providers. Cases included dysglycemic events identified from ED and hospital records (2016-2021). Controls were selected using incidence density sampling. Multiple CGM metrics were calculated among patients using CGM >70% of the time, using CGM data from two lookback periods (0-7 and 8-14 days) before each event. Generalized estimating equations were specified to estimate odds ratios and C-statistics. Results: Among 3626 CGM users, 108 patients had 154 hypoglycemic events and 165 patients had 335 hyperglycemic events. Approximately 25% of patients had no CGM data during either lookback; these patients had >2 × the odds of a hypoglycemic event and 3-4 × the odds of a hyperglycemic event. While several metrics were strongly associated with a dysglycemic event, none had good discrimination. Conclusion: Several CGM metrics were strongly associated with risk of dysglycemic events, and these can be used to identify higher risk patients. Also, patients who are not using their CGM device may be at elevated risk of adverse outcomes. However, no CGM metric or absence of CGM data had adequate discrimination to reliably provide actionable advance warning of an event and thus justify a rapid intervention.

Severe hypoglycemia and falls in older adults with diabetes: The Diabetes & Aging Study.

Objective: To estimate rates of severe hypoglycemia and falls among older adults with diabetes and evaluate their association. Research Design and Methods: Survey in an age-stratified, random sample adults with diabetes age 65-100 years; respondents were asked about severe hypoglycemia (requiring assistance) and falls in the past 12 months. Prevalence ratios (adjusted for age, sex, race/ethnicity) estimated the increased risk of falls associated with severe hypoglycemia. Results: Among 2,158 survey respondents, 79 (3.7%) reported severe hypoglycemia, of whom 68 (86.1%) had no ED visit or hospitalization for hypoglycemia. Falls were reported by 847 (39.2%), of whom 745 (88.0%) had no fall documented in outpatient or inpatient records. Severe hypoglycemia was associated with a 70% greater prevalence of falls (adjusted prevalence ratio = 1.7 (95% CI, 1.3-2.2)). Conclusion: While clinical documentation of events likely reflects severity or care-seeking behavior, severe hypoglycemia and falls are common, under-reported life-threatening events.

Tertiary prevention and treatment of rheumatic heart disease: a National Heart, Lung, and Blood Institute working group summary.

Although entirely preventable, rheumatic heart disease (RHD), a disease of poverty and social disadvantage resulting in high morbidity and mortality, remains an ever-present burden in low-income and middle-income countries (LMICs) and rural, remote, marginalised and disenfranchised populations within high-income countries. In late 2021, the National Heart, Lung, and Blood Institute convened a workshop to explore the current state of science, to identify basic science and clinical research priorities to support RHD eradication efforts worldwide. This was done through the inclusion of multidisciplinary global experts, including cardiovascular and non-cardiovascular specialists as well as health policy and health economics experts, many of whom also represented or closely worked with patient-family organisations and local governments. This report summarises findings from one of the four working groups, the Tertiary Prevention Working Group, that was charged with assessing the management of late complications of RHD, including surgical interventions for patients with RHD. Due to the high prevalence of RHD in LMICs, particular emphasis was made on gaining a better understanding of needs in the field from the perspectives of the patient, community, provider, health system and policy-maker. We outline priorities to support the development, and implementation of accessible, affordable and sustainable interventions in low-resource settings to manage RHD and related complications. These priorities and other interventions need to be adapted to and driven by local contexts and integrated into health systems to best meet the needs of local communities.

Racial and Ethnic Differences in the Association Between Mean Glucose and Hemoglobin A1c.

Background: Studies have reported significantly higher hemoglobin A1c (A1C) in African American patients than in White patients with the same mean glucose, but less is known about other racial/ethnic groups. We evaluated racial/ethnic differences in the association between mean glucose, based on continuous glucose monitor (CGM) data, and A1C. Methods: Retrospective study among 1788 patients with diabetes from Kaiser Permanente Northern California (KPNC) who used CGM devices during 2016 to 2021. In this study population, there were 5264 A1C results; mean glucose was calculated from 124,388,901 CGM readings captured during the 90 days before each A1C result. Hierarchical mixed models were specified to estimate racial/ethnic differences in the association between mean glucose and A1C. Results: Mean A1C was 0.33 (95% confidence interval: 0.23-0.44; P < 0.0001) percentage points higher among African American patients relative to White patients for a given mean glucose. A1C results for Asians, Latinos, and multiethnic patients were not significantly different from those of White patients. The slope of the association between mean glucose and A1C did not differ significantly across racial/ethnic groups. Variance for the association between mean glucose and A1C was substantially greater within groups than between racial/ethnic groups (65% vs. 9%, respectively). Conclusions: For African American patients, A1C results may overestimate glycemia and could lead to premature diabetes diagnoses, overtreatment, or invalid assessments of health disparities. However, most of the variability in the mean glucose-A1C association was within racial/ethnic groups. Treatment decisions driven by guideline-based A1C targets should be individualized and supported by direct measurement of glycemia.

Glycemic control and diabetes complications across health status categories in older adults treated with insulin or insulin secretagogues: The Diabetes & Aging Study.

BACKGROUND: For older adults with type 2 diabetes (T2D) treated with insulin or sulfonylureas, Endocrine Society guideline recommends HbA1c between 7% to <7.5% for those in good health, 7.5% to <8% for those in intermediate health, and 8% to <8.5% for those in poor health. Our aim was to examine associations between attained HbA1c below, within (reference), or above recommended target range and risk of complication or mortality. METHODS: Retrospective cohort study of adults ≥65 years old with T2D treated with insulin or sulfonylureas from an integrated healthcare delivery system. Cox proportional hazards models of complications during 2019 were adjusted for sociodemographic and clinical variables. Primary outcome was a combined outcome of any microvascular or macrovascular event, severe hypoglycemia, or mortality during 12-month follow-up. RESULTS: Among 63,429 patients (mean age: 74.2 years, 46.8% women), 8773 (13.8%) experienced a complication. Complication risk was significantly elevated for patients in good health (n = 16,895) whose HbA1c was above (HR 1.97, 95% CI 1.62-2.41) or below (HR 1.29, 95% CI 1.02-1.63) compared to within recommended range. Among those in intermediate health (n = 30,129), complication risk was increased for those whose HbA1c was above (HR 1.45, 95% CI 1.30-1.60) but not those below the recommended range (HR 0.99, 95% CI 0.89-1.09). Among those in poor health (n = 16,405), complication risk was not significantly different for those whose HbA1c was below (HR 0.98, 95% CI 0.89-1.09) or above (HR 0.96, 95% CI 0.88-1.06) recommended range. CONCLUSIONS: For older adults with T2D in good health, HbA1c below or above the recommended range was associated with significantly elevated complication risk. However, for those in poor health, achieving specific HbA1c levels may not be helpful in reducing the risk of complications.

Opioids and Chronic Pain: Impact of the NIH Pathways to Prevention Evidence-Based Workshop Program.

The National Institutes of Health (NIH) Office of Disease Prevention (ODP) sponsors Pathways to Prevention (P2P), an evidence-based scientific workshop program that helps advance prevention research. Each P2P workshop is presided over by an independent expert panel and informed by a systematic evidence review, scientific presentations, and public input. Post-workshop activities include collaborating with federal agency partners to develop an action plan for addressing key research gaps. Primary outcomes of P2P workshops include developing a research agenda and creating or enhancing initiatives to implement the agenda. In 2014, ODP partnered with the NIH Pain Consortium and two NIH institutes to convene "The Role of Opioids in the Treatment of Chronic Pain." This workshop assessed the state-of-the-science on the long-term effectiveness, safety, and harms of opioid use for managing chronic pain. In 2021, ODP initiated an assessment of the outcomes and impact of the Opioids P2P workshop. We applied an evaluation framework and a mixed methods approach encompassing web analytics, bibliometric assessment, grant portfolio analysis, policy assessment, and key informant interviews. Our data showed that the workshop attracted a broad audience, and its published reports had high impact. The workshop also helped inform over 100 new research projects through grants funded by three federal agencies, as well as national legislation and practice guidelines from influential organizations. In sum, the Opioids P2P workshop and follow-up activities have identified gaps in scientific knowledge, informed clinical practice, and catalyzed change on a national level for addressing the prescription opioid crisis.

Development and Validation of the Life Expectancy Estimator for Older Adults with Diabetes (LEAD): the Diabetes and Aging Study.

BACKGROUND: Estimated life expectancy for older patients with diabetes informs decisions about treatment goals, cancer screening, long-term and advanced care, and inclusion in clinical trials. Easily implementable, evidence-based, diabetes-specific approaches for identifying patients with limited life expectancy are needed. OBJECTIVE: Develop and validate an electronic health record (EHR)-based tool to identify older adults with diabetes who have limited life expectancy. DESIGN: Predictive modeling based on survival analysis using Cox-Gompertz models in a retrospective cohort. PARTICIPANTS: Adults with diabetes aged ≥ 65 years from Kaiser Permanente Northern California: a 2015 cohort (N = 121,396) with follow-up through 12/31/2019, randomly split into training (N = 97,085) and test (N = 24,311) sets. Validation was conducted in the test set and two temporally distinct cohorts: a 2010 cohort (n = 89,563; 10-year follow-up through 2019) and a 2019 cohort (n = 152,357; 2-year follow-up through 2020). MAIN MEASURES: Demographics, diagnoses, utilization and procedures, medications, behaviors and vital signs; mortality. KEY RESULTS: In the training set (mean age 75 years; 49% women; 48% racial and ethnic minorities), 23% died during 5 years follow-up. A mortality prediction model was developed using 94 candidate variables, distilled into a life expectancy model with 11 input variables, and transformed into a risk-scoring tool, the Life Expectancy Estimator for Older Adults with Diabetes (LEAD). LEAD discriminated well in the test set (C-statistic = 0.78), 2010 cohort (C-statistic = 0.74), and 2019 cohort (C-statistic = 0.81); comparisons of observed and predicted survival curves indicated good calibration. CONCLUSIONS: LEAD estimates life expectancy in older adults with diabetes based on only 11 patient characteristics widely available in most EHRs and claims data. LEAD is simple and has potential application for shared decision-making, clinical trial inclusion, and resource allocation.

An electronic medical record (EMR) prompt improves screening rates for metabolic conditions among children with obesity.

OBJECTIVE: This study evaluated the effectiveness of an automated prompt in the electronic medical record (EMR) to increase screening rates for metabolic conditions and referrals to health education and to improve BMI percentile among children with obesity. METHODS: The intervention used an EMR reminder that provided a panel of lab orders (hemoglobin A1c, lipid panel, and alanine aminotransferase) during clinical encounters among pediatric patients ages 10 to 18 with BMI ≥ 95th percentile. Data on demographics, comorbid conditions, BMI, lab results, and health education referrals were analyzed. Cohorts during the year before (n = 3479) and after (n = 3439) workflow implementation were compared. RESULTS: The distribution of race/ethnicity among children with obesity was 56% Hispanic, 19% White, 11% Filipino, 4% Pacific Islander, 3% Black, and 1% East/South Asian. Orders for metabolic lab tests increased from 2% in the pre-workflow period to 52% in the post-workflow period (p < 0.0001). Completed screening rates improved from 1% to 27% (p < 0.0001). Health education referrals increased from 0.4% to 7% (p < 0.0001). We observed a mean change in BMI percentile of -0.13% (p = 0.06). CONCLUSIONS: This study validates the use of an EMR-based prompt to improve metabolic lab screening and health education referrals among children with obesity. During the limited period of follow-up, we found no significant change in BMI percentile.

Validation of a Hypoglycemia Risk Stratification Tool Using Data From Continuous Glucose Monitors.

This cohort study uses data from continuous glucose monitoring to validate a hypoglycemia risk stratification tool.

Quality control ensures fidelity in ribosome assembly and cellular health.

The coordinated integration of ribosomal RNA and protein into two functional ribosomal subunits is safeguarded by quality control checkpoints that ensure ribosomes are correctly assembled and functional before they engage in translation. Quality control is critical in maintaining the integrity of ribosomes and necessary to support healthy cell growth and prevent diseases associated with mistakes in ribosome assembly. Its importance is demonstrated by the finding that bypassing quality control leads to misassembled, malfunctioning ribosomes with altered translation fidelity, which change gene expression and disrupt protein homeostasis. In this review, we outline our understanding of quality control within ribosome synthesis and how failure to enforce quality control contributes to human disease. We first provide a definition of quality control to guide our investigation, briefly present the main assembly steps, and then examine stages of assembly that test ribosome function, establish a pass-fail system to evaluate these functions, and contribute to altered ribosome performance when bypassed, and are thus considered "quality control."

Corrigendum: Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases.

[This corrects the article DOI: 10.3389/fimmu.2022.865241.].