Notes

Teleology very first: Ambitions before knowledge as well as notion.
To illustrate a method that accounts for sampling variation in identifying suppliers and counties with outlying rates of a particular pattern of inconsistent billing for ambulance services to Medicare.

US Medicare claims for a 20% simple random sample of 2010-2014 fee-for-service beneficiaries.

We identified instances in which ambulance suppliers billed Medicare for transporting a patient to a hospital, but no corresponding hospital visit appeared in billing claims. We estimated the distributions of outlier supplier and county rates of such "ghost rides" by fitting a nonparametric empirical Bayes model with flexible distributional assumptions to account for sampling variation.

We included Basic and advanced life support ground emergency ambulance claims with a hospital destination.

"Ghost ride" rates varied considerably across both ambulance suppliers and counties. We estimated 6.1% of suppliers and 5.0% of counties had rates that exceeded 3.6%, which was twice the national average of "ghost rides" (1.8% of all ambulance transports).

Health care fraud and abuse are frequently asserted but can be difficult to detect. Our data-driven approach may be a useful starting point for further investigation.
Health care fraud and abuse are frequently asserted but can be difficult to detect. Our data-driven approach may be a useful starting point for further investigation.Adverse drug reactions (ADRs) are a major concern for patients, clinicians, and regulatory agencies. The discovery of serious ADRs leading to substantial morbidity and mortality has resulted in mandatory phase IV clinical trials, black box warnings, and withdrawal of drugs from the market. Real-world data, data collected during routine clinical care, is being adopted by innovators, regulators, payors, and providers to inform decision making throughout the product life cycle. We outline several different approaches to modern pharmacovigilance, including spontaneous reporting databases, electronic health record monitoring and research frameworks, social media surveillance, and the use of digital devices. Some of these platforms are well-established while others are still emerging or experimental. Pyrrolidinedithiocarbamate ammonium clinical trial We highlight both the potential opportunity, as well as the existing challenges within these pharmacovigilance systems that have already begun to impact the drug development process, as well as the landscape of postmarket drug safety monitoring. Further research and investment into different and complementary pharmacovigilance systems is needed to ensure the continued safety of pharmacotherapy.
To determine the efficacy of antibody typing and treatment on live birth rate in Chinese patients with antiphospholipid syndrome (APS)-related recurrent spontaneous abortion (RSA).

A retrospective study analyzed 4542 Chinese patients who experienced spontaneous abortion, of whom 314 had APS (272 primary and 42 secondary). Type of antibodies was tested. Anticoagulant and anti-inflammatory treatments were adopted according to the titer and type of antibodies. The incidence of repeated abortion and placental dysfunction, gestational age, and mean weight of the fetuses were recorded.

Among the patients with APS-related RSA, primary APS accounted for the largest proportion. The proportion of antibody classification was as follows β2-glycoprotein 1 (β2GP1)-IgM (151, 48.08%), lupus anticoagulant (LAC) (36, 11.46%), anticardiolipin (aCL)-IgM (32, 10.19%), β2GP1-IgM and aCL-IgM (29, 9.23%), and aCL-IgG (16, 5.09%). After treatment, the negative conversion of antibody, including β2GP1-IgM and LAC, significantly improved pregnancy outcomes. There was no significant difference in pregnancy outcomes between the other antibody titers.

The combination of anticoagulant and anti-inflammatory treatment led to a higher live birth rate in the treatment of APS-related RSA, highlighting the potential of antibody typing in providing clinical guidance for the treatment of APS-related RSA.
The combination of anticoagulant and anti-inflammatory treatment led to a higher live birth rate in the treatment of APS-related RSA, highlighting the potential of antibody typing in providing clinical guidance for the treatment of APS-related RSA.Clostridioides difficile infections (CDI) result from antibiotic use and cause severe diarrhea which is life threatening and costly. A specific probiotic containing Lactobacillus acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 has demonstrated a strong inhibitory effect on the growth of several nosocomial C. difficile strains by production of antimicrobial metabolites during fermentation. Though there are several lactobacilli shown to inhibit C. difficile growth by processes relying on acidification, this probiotic has demonstrated potency for CDI prevention among hospitalized patients. Here, we describe the acid-dependent and independent mechanisms by which these strains impair the cytotoxicity of a hypervirulent strain, C. difficile R20291 (CD). These bacteria were co-cultured in a series of experiments under anaerobic conditions in glucose-rich and no-sugar medium to inhibit or stimulate CD toxin production, respectively. In glucose-rich medium, there was low CD ted patients compared with other probiotic formulae.
Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools.

This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.
This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.
5' adenosine monophosphate-activated kinase (AMPK) is an essential regulator of cellular energy homeostasis and has been associated with different pathologies, including cancer. Precisely defining the biological role of AMPK necessitates the availability of a potent and selective inhibitor.

High-throughput screening and chemical optimization were performed to identify a novel AMPK inhibitor. Cell proliferation and mechanistic assays, as well as gene expression analysis and chromatin immunoprecipitation were used to investigate the cellular impact as well as the crosstalk between lipid metabolism and androgen signaling in prostate cancer models. Also, fatty acid turnover was determined by examining lipid droplet formation.

We identified BAY-3827 as a novel and potent AMPK inhibitor with additional activity against ribosomal 6 kinase (RSK) family members. It displays strong anti-proliferative effects in androgen-dependent prostate cancer cell lines. Analysis of genes involved in AMPK signaling revealed thibitor BAY-3827 will contribute to a better understanding of the role of AMPK signaling in cancer, especially in prostate cancer.
Workplace-based assessment in competency-based medical education employs entrustment-supervision scales to suggest trainee competence. However, clinical supervision involves many factors and entrustment decision-making likely reflects more than trainee competence. We do not fully understand how asupervisor's impression of trainee competence is reflected in their provision of clinical support. We must better understand this relationship to know whether documenting level of supervision truly reflects trainee competence.

We undertook acollective case study of supervisor-trainee dyads consisting of attending internal medicine physicians and senior residents working on clinical teaching unit inpatient wards. We conducted field observations of typical daily activities and semi-structured interviews. Data was analysed within each dyad and compared across dyads to identify supervisory behaviours, what triggered the behaviours, and how they related to judgments of trainee competence.

Ten attending physician-seni This has direct implications for entrustment assessments tying competence to supervisory behaviours, because supervision is complex. Workplace-based assessments that capture narrative data including the rationale for supervisory behaviours may lead to deeper insights than numeric entrustment ratings.
Due to the COVID-19 pandemic, clinical rotations at the University of Michigan Medical School (UMMS) were suspended on March17, 2020, per the Association of American Medical Colleges' recommendations. No alternative curriculum existed to fill the educational void for clinical students. The traditional approach to curriculum development was not feasible during the pandemic as faculty were redeployed to clinical care, and the immediate need for continued learning necessitated anew model.

One student developed an outline for an online course on pandemics based on peer-to-peer conversations regarding learners' interests and needs, and she proposed that students author the content given the immediate need for acurriculum. Fifteen student volunteers developed content to fill knowledge gaps, and expert faculty reviewers confirmed that the student authors had successfully curated acomprehensive curriculum.

The crowdsourced student content coalesced into a40-hour curriculum required for all 371 clinical-level students at UMMS. This student-driven effort took just 17days from outline to implementation, and the final product is afull course comprising five modules, multiple choice questions, discussion boards, and assignments. Learners were surveyed to gauge success, and 93% rated this content as relevant to all medical students.

The successful implementation of this model for curriculum development, grounded in the Master Adaptive Learner framework, suggests that medical students can be entrusted as stewards of their own education. As we return to apost-pandemic "normal," this approach could be applied to the maintenance and de novo development of future curricula.
The successful implementation of this model for curriculum development, grounded in the Master Adaptive Learner framework, suggests that medical students can be entrusted as stewards of their own education. As we return to a post-pandemic "normal," this approach could be applied to the maintenance and de novo development of future curricula.
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