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The Institute for Healthcare Improvement challenges clinicians and administrators to raise care quality through its 5 Million Lives Campaign, a sequel to the 100,000 Lives Campaign. Here, review a case study on the importance of postoperative monitoring of opioid-naive patients who are receiving narcotics. [ABSTRACT FROM AUTHOR]

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele. [ABSTRACT FROM AUTHOR]

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. This study examines whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery disease (CAD). In a randomized prospective, double-blind, crossover, and placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800 to 1,200 mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period, and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation, platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity (TF-PCA), and adhesion molecule density were assessed before and after each phase. PDT was evaluated by an ex vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35% in patients who received magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD. [ABSTRACT FROM AUTHOR]

Signal Amplification by Reversible Exchange (SABRE) is a relatively simple and fast hyperpolarization technique that has been used to hyperpolarize the α-ketocarboxylate pyruvate, a central metabolite and the leading hyperpolarized MRI contrast agent. In this work, we show that SABRE can readily be extended to hyperpolarize 13C nuclei at natural abundance on many other α-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P13C=17%) and 2-oxobutyrate (P13C=25%) with alkyl chains in the R-group, oxaloacetate (P13C=11%) and alpha-ketoglutarate (P13C=13%) with carboxylate moieties in the R group, and phenylpyruvate (P13C=2%) and phenylglyoxylate (P13C=2%) with phenyl rings in the R-group. New catalytically active SABRE binding motifs of the substrates to the hyperpolarization transfer catalyst-particularly for oxaloacetate-are observed. We experimentally explore the connection between temperature and exchange rates for all of these SABRE systems and develop a theoretical kinetic model, which is used to fit the hyperpolarization build-up and decay during SABRE activity., (© 2024 Wiley‐VCH GmbH.)

This study examined day-level associations between trouble sleeping and three cannabis-use indices (likelihood/quantity of use and impaired control). We evaluated behavioral and cognitive mediators of the association between trouble sleeping and cannabis outcomes. Youth ( N = 86, ages 15-24, 48.8% female, 58.8% White, 18.6% Latine) who regularly used cannabis were recruited for an intervention study. This preregistered secondary data analysis leveraged data from a 1-week ecological momentary assessment (EMA) study completed prior to intervention. Trouble sleeping, cannabis use, and impaired control over use were assessed each morning; negative affect, risk-taking propensity, and cannabis craving were assessed multiple times and aggregated to create a daily average. Multilevel structural equation modeling evaluated hypothesized temporally sequenced associations and putative mechanisms at the day (i.e., within) and person (i.e., between) level. In bivariate analyses at the person level, there were large-effect associations between trouble sleeping and craving and negative affect, and between craving and cannabis-use likelihood and quantity (rs from .34 to .48). In multilevel analyses at the day level, participants were less likely to use cannabis the next day after reporting more trouble sleeping (β = -.65, p < .001). Trouble sleeping was not directly associated with subsequent cannabis-use quantity or impaired control, or indirectly via negative affect, risk-taking propensity, or craving. Trouble sleeping had differential relations with cannabis-use indices at the day and person levels. To promote youth health and reduce cannabis use, future research may consider the unique, person- and situation-driven mechanistic processes at play. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Endometrial cancer (EC) is the only gynecologic malignancy showing increasing trends in incidence and mortality. While standard treatment has been effective primarily for early-stage EC, precision medicine with tailored therapy has revolutionized the management of this disease. Genome sequencing analyses have identified four sub-types of EC. Treatments for primary and metastatic disease can now be tailored more accurately to achieve better oncologic results., Areas Covered: This review provides an overview of the most relevant and updated evidence in the literature regarding EC molecular analysis and its role in risk classification, prognostication, and guidance for tailored and target therapies in early and advanced/metastatic stages. In addition, it provides updated information on optimal surgical management based on molecular classification and highlights key advances and future strategies., Expert Opinion: EC molecular analysis yields the potential of tailoring adjuvant treatment by escalating or deescalating therapy, as shown for POLE-mutated and p53-mutated tumors. Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.

Epidermal keratinocytes form the first-line cellular barrier of the skin for protection against external injuries and maintenance of local tissue homeostasis. Expression of ZBP1 was shown to cause necroptotic keratinocyte cell death and skin inflammation in mice. We sought to characterize the relevance of ZBP1 and necroptosis in human keratinocytes and type 1-driven cutaneous acute graft-versus-host disease. in this study, we identify ZBP1 expression, necroptosis, and interface dermatitis as being the hallmarks of acute graft-versus-host disease. ZBP1 expression was dependent on leukocyte-derived IFNγ, and interference with IFNγ signaling by Jak inhibition prevented cell death. In predominantly IL-17-driven psoriasis, both ZBP1 expression and necroptosis could not be detected. Of note, in contrast to the signaling in mice, ZBP1 signaling in human keratinocytes was not affected by RIPK1's presence. These findings show that ZBP1 drives inflammation in IFNγ-dominant type 1 immune responses in human skin and may further point to a general role of ZBP1-mediated necroptosis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol use is common among adolescents and young adults (AYA) and linked to poor sleep quality. Poor sleep quality may also increase alcohol use and alcohol craving, yet bi-directional relations between sleep quality and AYA alcohol use are poorly understood., Purpose: This study examined bi-directional associations between sleep quality, alcohol craving, and alcohol use in AYA using ecological momentary assessment (EMA) and explored if biological sex, age, or race moderated these associations., Methods: This pre-registered secondary analysis pooled EMA data from the baseline, pre-randomization period (M = 8.18 days, range = 1-17) in two double-blind randomized placebo-controlled clinical trials examining medication effects on alcohol use in AYA (N = 115). Each morning, participants reported sleep quality and alcohol consumption (i.e., number of standard drinks) from the previous day, and craving was rated at several random points each day., Results: Multilevel modeling showed that poorer average sleep quality was associated with higher levels of alcohol craving for females but not for males, and better overall levels of sleep quality were associated with decreased likelihood of engaging in alcohol use. No other person- or day-level associations between sleep and alcohol use emerged., Conclusions: Better sleep quality may be protective against alcohol use in AYA, and female AYA who report poorer sleep quality may experience higher levels of alcohol craving. Research and clinical assessment of AYA sleep quality can contribute to understanding of factors promoting alcohol craving and use., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Greater discrepancies between parent and adolescent reports of parenting behaviors are associated with poorer adolescent functioning. The present research aims to build from the existing literature by examining unique parent and adolescent perceptions of parental monitoring and distinct sources of parental knowledge (i.e, parental solicitation, parental control, child disclosure) and their association with adolescent cannabis and alcohol use and disorder symptoms using cross-sectional data., Method: Parent-adolescent dyads ( N = 132) were recruited from the community and the family court system. Adolescents were ages 12 to 18 (40.2% female; 68.2% White, 18.2% Hispanic). Parents and adolescents completed a questionnaire assessing the four domains of parenting behaviors. Adolescents' substance-use behaviors and related disorder symptoms were assessed via adolescent self-report and semi-structured interviews., Results: Parental ratings of distinct parenting behaviors were higher (more favorable) than their child's reports, as shown in prior studies. Parent-reported parenting behaviors were uniquely related to cannabis use, over and above adolescent reports and the adolescent's age. With regard to report discrepancies, interactive effects of parent and adolescent perceptions of parental control were not statistically significant in our analysis after correcting for multiple tests., Conclusions: While most research relating parental monitoring to adolescent cannabis use relies solely on adolescent perceptions, our study suggests a unique role of parent perceptions for cannabis use and disorder symptoms, respectively. Findings support the importance of considering unique parent and adolescent perceptions of what parents know, as well as how they know it, to understand early cannabis use and problem development., Competing Interests: We have no conflict of interest to disclose.

Purpose: Hospital pharmacists contribute to patient safety and quality initiatives by overseeing the prescribing of antidiabetic medications. A pharmacist-driven glycemic control protocol was developed to reduce the rate of severe hypoglycemia events (SHE) in high-risk hospitalized patients. Methods: We retrospectively analyzed the rates of SHE (defined as blood glucose ≤40 mg/dL), before and after instituting a pharmacist-driven glycemic control protocol over a 4-year period. A hospital glucose management team that included a lead Certified Diabetes Educator Pharmacist (CDEP), 5 pharmacists trained in diabetes, a lead hospitalist, critical care and hospital providers established a process to first identify patients at risk for severe hypoglycemia and then implement our protocol. Criteria from the American Diabetes Association and the American Association of Clinical Endocrinologists was utilized to identify and treat patients at risk for SHE. We analyzed and compared the rate of SHE and physician acceptance rates before and after protocol initiation. Results: From January 2015 to March 2019, 18 297 patients met criteria for this study; 139 patients experienced a SHE and approximately 80% were considered high risk diabetes patients. Physician acceptance rates for the new protocol ranged from 77% to 81% from the year of initiation (2016) through 2018. The absolute risk reduction of SHE was 9 events per 1000 hospitalized diabetic patients and the relative risk reduction was 74% SHE from the start to the end of the protocol implementation. Linear regression analysis demonstrated that SHE decreased by 1.5 events per 1000 hospitalized diabetic patients (95% confidence interval, -1.54 to -1.48, P  < .001) during the 2 years following the introduction of the protocol. This represents a 15% relative reduction of SHE per year. Conclusion: The pharmacist-driven glycemic control protocol was well accepted by our hospitalists and led to a significant reduction in SHE in high-risk diabetes patient groups at our hospital. It was cost effective and strengthened our physician-pharmacist relationship while improving diabetes care., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Current evidence regarding the optimal length of hospital stay (LOS) following myocardial infarction (MI) is limited. This study aimed to examine LOS policy for MI patients and to assess the safety of early discharge., Methods: A prospective observational study that included patients with STEMI and NSTEMI enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients were divided into three subgroups according to their LOS: <3 days (short-LOS), 3-6 days (intermediate-LOS) and >6 days (long-LOS). We compared baseline characteristics, management strategies and clinical outcomes at 30 days and 1 year in these groups., Results: Ten thousand four hundred and fifty eight patients were enrolled in the study. The LOS of MI patients gradually decreased over time. Short-LOS and intermediate-LOS patients had similar clinical characteristics while patients in the long-LOS group were older with more co-morbidity. There was no difference in the clinical outcomes, including re-MI, arrhythmias, 30 days MACE, and 30 days mortality between the short-LOS and intermediate-LOS groups. However, the rate of re-hospitalizations was higher in the short-LOS group (20.9% vs. 17.8%, p = .004) without evidence of increased cardiovascular events. In multivariate analysis, the LOS did not predict either 30 days mortality (HR: 1.3; CI:0.45-5.48), nor MACE at 30 days (HR: 1.1; CI:0.79-1.56)., Conclusion: Our study suggests that an early discharge strategy of up to 3 days from admission is safe for low and intermediate-risk patients after both STEMI and NSTEMI. Nevertheless, this strategy is associated with an increased risk of potential avoidable readmission and there might be psychological and social factors that may warrant a longer stay., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Sepsis is a severe life-threatening syndrome caused by dysregulated host responses to infection. Biomarkers that allow for monitoring the patient's immune status are needed. Recently, a flow cytometry-based detection of in vivo inflammasome activation by formation of cytoplasmic aggregates of ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) has been proposed. Here we report on the frequency of ASC-speck + leukocytes correlating with the survival of sepsis. 25 patients with sepsis were sampled consecutively for 7 days. Blood, serum samples and patient data were collected according to the guidelines of the PredARRT-Sep-Trial. Flow cytometric analysis was performed on fresh whole blood samples to investigate the formation of ASC-specks in leukocyte subsets. Serum samples were analyzed for production of IL-1ß, IL-18 and additional inflammatory markers. ASC-speck formation was found to be increased in leukocytes from sepsis patients compared to healthy donor controls. The absolute number of ASC-speck + neutrophils peaked on day 1. For monocytes, the highest percentage and maximum absolute number of ASC-speck + cells were detected on day 6 and day 7. Inflammatory cytokines were elevated on day 1 and declined thereafter, with exception of IL-18. Survival analysis showed that patients with lower absolute numbers of ASC-speck + monocytes (<1,650 cells/ml) on day 6 had a lower probability to survive, with a hazard ratio (HR) of 10.178. Thus, the frequency of ASC-speck + monocytes on day 6 after onset of sepsis may serve to identify patients at risk of death from sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cui, Oehrl, Ahmad, Brenner, Uhle, Nusshag, Rupp, Funck, Meisel, Weigand, Morath and Schäkel.)

Purpose: The heightened involvement of government organizations to improve pain management and mitigate opioid adverse events brings to light the need for an opioid stewardship model. Summary: The US opioid epidemic has resulted in new hospital requirements for pain management by regulatory agencies. Opioid stewardship is a concept in the early development stage of pharmacy practice. There exists a need for a cohesive vision of opioid stewardship and the role of the pharmacist. Over the course of 17 years, the tracks for opioid stewardship in Fairview Health Services were laid through numerous initiatives to mitigate adverse events and improve the quality of pain management. This article will describe a transformation process for establishing the framework for opioid stewardship within Fairview Health Services and role of the pharmacist. Conclusions: The vision for opioid stewardship will ultimately be defined through the actions taken to improve quality care and patient safety. Opioid safety should be expanded to include stewardship of approaches that reduce the risk of diversion, overdose, and medication abuse. Pharmacists currently have a major role monitoring opioid medication in hospitals and this component will increase with new regulatory requirements., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis., Methods: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome., Results: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors., Conclusions: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)