INFORMER and Potassium Values: A system to enhance detection, notification, and action upon a threat to patient safety in the emergency department [abstract]

Computational Infrastructure and Informatics Poster SessionBackground: Quick remediation should occur after critically abnormal potassium levels are detected by the medical laboratory in blood from emergency department (ED) patients. Critical potassium levels can be elevated (“HyperK+“) or decreased (“HypoK+“). HyperK+ and HypoK+ can both lead to avoidable patient harm by causing heart rhythm problems, which can be harmful or lethal. Also, Continuous Quality Improvement (CQI) could be enhanced by the creation of an electronic “audit trail” to track these remediations, which involve detection, notification, action-upon, and documentation steps (D1-N-A-D2). HyperK+ and HypoK+ are a logical first target to ameliorate inefficiencies of D1-N-A-D2, because of the frequency of occurrence of these problems in the ED, because the appropriate rapid ED response is clear, and because failures of D1-N-A-D2. can hurt or kill patients. Hypothesis: An automated D1-N-A-D2, plus audit path, can be created, then merged with a to-be-created standing ED order set, to hasten the treatment of HyperK+ and HypoK+. Methods: (1) A standing order set will be adopted, to permit nurses to administer appropriate treatments to patients with either HyperK+ or HypoK+, without prior physician notification. Oral or intravenous potassium, as appropriate, will remediate HypoK+, Administration of insulin plus glucose, calcium, sodium bicarbonate, and sodium polystyrene resin will ameliorate HyperK+. Order sets will be created after input from physician and nursing personnel. (Re-obtaining of blood from patients in whom HyperK+ is thought to be a false positive result, due to hemolysis of the blood sample, will be permitted). (2) “Electronic loop”: Engineers will create an electronic pathway to enable the rapid electronic notification of appropriate medical personnel, after critical HyperK+ or HypoK+ have been detected. This will enable and drive nurses to action. Actions can be electronically audited via review of digital PyxisTM medication administration machine records, matching medication withdrawals for specific patients to specific incidences of HyperK+ and HypoK+. Time to nurse action will be documented. Data during implementation of D1-N-A-D2 will be compared to prior historical control data, to determine whether the newly created process delivers appropriate care more quickly to patients with critically abnormal K+ values. (In addition, it is anticipated that electronic review of laboratory data for the historical controls will reveal total system failures for some patients; some patients with HyperK+ and/or HypoK+ might not have been treated at all for their potassium abnormality during their time in the ED.) Results: Time to treatment for HyperK+ and HypoK+ patients, and % of patients with HyperK+ and HypoK+ who represent total system failures, before vs. after implementation of the pervasive computing protocol, will be determined. Conclusion: It is anticipated that a pervasive computing environment can be created to facilitate implementation of a standing medication order set, to enable more rapid D1-N-A-D2 after critical values of HyperK+ or HypoK+ are detected in the blood of emergency department patients. Also, this environment will decrease the failure-to-treat rate for critical HyperK+ and HypoK+

INFORMER: A System for Immediate and Direct Notification of Critical Data for Patient Care [abstract]

Computational Infrastructure and Informatics Poster SessionEfficient and timely delivery of healthcare requires constant improvements in the quality while keeping the cost of delivery under control. One of the important requirements for such delivery system is the timely notification of patient related data (For example notification of laboratory results on metabolites, circulating levels of certain medications, etc) to doctors, nurses, and other medical professionals for prescribing necessary action. Currently, in nearly all hospitals and laboratories, laboratory or nursing staff are responsible for manually transmitting such information. They take the information verbally or written on a piece of paper, on a pad or on some other media to the recipient in one or multiple hops. Such approach, although serves the purpose, has a number of ordinary to serious limitations such as a higher error rate, incorrect destination, security breach, etc., that could endanger patients life. For example, it is quite possible that the person responsible for notification may forget or delay, for a variety of reasons, to notify the doctor or medical staff or may miscommunicate the results; for example instead of sodium of 150, he or she may orally communicate it as 160. It is also possible that the dispatcher may deliver the information to wrong person (security breach), or take too long to deliver the information. These issues are likely to have serious consequences, in particular for institutions that deal with human subjects such as emergency department of the hospitals where rapid notification is essential for saving lives of critically ill patients. For results communication, paging is a commonly used notification methods but it also involves human and any inadvertent delays in reporting critical data to the physician and other medical staff or to the patient can have serious consequences. We claim that automation in data notification will (a) eliminate or minimize such undesirable consequences, (b) will keep the cost down and (c) improve patient care. We are in the process of designing a pervasive system, referred here as “Informer” to automate the notification process. The system will (a) compose the information (test results, recommendations, etc.) to be dispatched in a easy to read format, (b) identify and notify the critical results to the right medical professionals, (b) maintain an active log of automation process for immediate reference, (c) guarantee accurate data delivery, (d) keep the cost down, (e) provide necessary security, (f) work equally well with wired and wireless network, and (g) offer a high scalability. It will be (a) an independent system with plug and play capability, (b) can port to any system (window, Mac, Linux, etc.), and (c) easy to configure for specific needs

Development of a Capillary Blood Mail-in Kit for the Measurement of Hemoglobin A1c

Biomedical Tissue Engineering, Biomaterials and Medical Devices Poster SessionIt is estimated that in the United States diabetes affects 25 million children and adults, and is a major cause of morbidity and mortality. Cost of diabetes in the United States is over $175 billion a year. To optimize insulin dose diabetic patients regularly measure their blood glucose. Random glucose measurement does not provide indication of long-term glucose control. The long-term indicator of glucose control is the hemoglobin A1c (HbA1c). It provides average blood glucose level of the previous 2 to 3 months. In most cases, for HbA1c testing, patients come to clinical laboratories for blood draw. It is time consuming and inconvenient. In recent years efforts have been made to develop sample mail-in kit where the blood sample can be collected at home and mailed to a testing laboratory. We present the development of a stabilizing solution (SS) and mail-in kit for Hb A1c testing. With this kit, after a simple finger prick, a patient collects blood using a capillary tube. The blood-containing capillary tube is dropped in a tube containing SS, and is mailed to the laboratory in a pre-stamped box in a regular mail. Validation of the kit included 1) Comparing HbA1c levels in the whole blood to hemolysate and SS immediately after preparation of the samples, 2) Stability of HbA1c in SS for 4 and 7 days at 4oC, room temperature and 37oC, 3) mailing the samples in the regular mail and comparing the values of HbA1c in mailed-in samples to the whole blood samples. The data for some of these comparisons are shown in the Table below. No significant difference was found in the values of HbA1c in various test groups. In conclusion, we have developed a convenient mail-in kit for the measurement of HbA1c. The advantages of mail-in kit for HbA1c measurement include patients' satisfaction as it negates the need for venipuncture and laboratory visit for sample collection, and the availability of results to a physician before the patient's visit for optimal care

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer : A signature step hinting towards clinical perfection

Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids can enhance drug sensitivity and suppress proliferation, metastasis, and angiogenesis of cancer cells by modulating several oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation of various biological and pathological processes, including various cancers. In the present review, the structure, chemistry and miR targeting efficacy of quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, and cyanidin against several cancer types are comprehensively discussed. miRs are considered as next-generation medicine of recent times, and their targeting by naturally occurring flavonoids in cancer cells could be deemed as a signature step. We anticipate that our compilations related to miRNA-mediated regulation of cancer cells by flavonoids might catapult the clinical investigations and affirmation in the future