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The objective of this study is to explore the role of the SDF-1α/CXCR4 pathway in the development of intracranial aneurysm (IA) induced by hemodynamic forces. We collected 12 IA and six superficial temporal artery samples for high-throughput sequencing, hematoxylin and eosin staining, and immunohistochemistry to examine vascular remodeling and determine the expression of the components of the SDF-1α/CXCR4 pathway, structural proteins (α-SMA and calponin) of vascular smooth muscle cells (VSMCs), and inflammatory factors (MMP-2 and TNF-α). Computational fluid dynamics (CFD) was used for hemodynamic analysis. Mouse IA model and dynamic co-culture model were established to explore the mechanism through which the SDF-1α/CXCR4 pathway regulates the phenotypic transformation of VSMCs in vivo and in vitro. We detected a significant elevation of SDF-1α and CXCR4 in IA, which was accompanied by vascular remodeling in the aneurysm wall (i.e., the upregulation of inflammatory factors, MMP-2 and TNF-α, and the downregulation of contractile markers, α-SMA and calponin). In addition, hemodynamic analysis revealed that compared with unruptured aneurysms, ruptured aneurysms were associated with lower wall shear stress and higher MMP-2 expression. In vivo and in vitro experiments showed that abnormal hemodynamics could activate the SDF-1α/CXCR4, P38, and JNK signaling pathways to induce the phenotypic transformation of VSMCs, leading to IA formation. Hemodynamics can induce the phenotypic transformation of VSMCs and cause IA by activating the SDF-1α/CXCR4 signaling pathway.

After decades of liberal opioid prescribing, multiple efforts have been made to reduce reliance upon opioids in clinical care. Little is known about the effects of opioid prescribing policies on outcomes beyond opioid prescribing.

To evaluate the combined effects of multiple opioid prescribing policies implemented in a safety-net primary care clinic in San Francisco, CA, in 2013-2014.

Retrospective cohort study and conditional difference-in-differences analysis of nonrandomized clinic-level policies.

273 patients prescribed opioids for chronic non-cancer pain in 2013 at either the treated (n=151) or control clinic (n=122) recruited and interviewed in 2017-2018.

Policies establishing standard protocols for dispensing opioid refills and conducting urine toxicology testing, and a new committee facilitating opioid treatment decisions for complex patient cases.

Opioid prescription (active prescription, mean dose in morphine milligram equivalents [MME]) from electronic medical charts, and heroin and opiescribing with potential harms from rapid change.

Clinic-level opioid prescribing policies were associated with reduced dose, although the control clinic achieved similar reductions by the fourth post-policy year, and the policies may have been associated with increased non-prescribed opioid analgesic use. Clinicians should balance the urgency to reduce opioid prescribing with potential harms from rapid change.

Polypharmacy is associated with the increased use of potentially inappropriate medications, where the risks of medicine use outweigh its benefits. Stopping medicines (deprescribing) that are no longer needed can be beneficial to reduce the risk of adverse events. We summarized the willingness of patients and their caregivers towards deprescribing.

A systematic search was conducted in four databases from inception until April 30, 2021 as well as search of citation of included articles. Studies that reported patients' and/or their caregivers' attitude towards deprescribing quantitatively were included. All studies were independently screened, reviewed, and data extracted in duplicates. Simvastatin Patients and caregivers willingness to deprescribe their regular medication was pooled using random effects meta-analysis of proportions.

Twenty-nine unique studies involving 11,049 participants were included. All studies focused on the attitude of the patients towards deprescribing, and 7 studies included caregivers' perspsf.io/fhg94.

Most patients and their caregivers were willing to deprescribe their medications, whenever possible and thus should be offered a trial of deprescribing. Nevertheless, as these tools have a poor predictive ability, patients and their caregivers should be engaged during the deprescribing process to ensure that the values and opinions are heard, which would ultimately improve patient safety. In terms of limitation, as not all studies may published the methods and results of measurement they used, this may impact the methodological quality and thus our findings. OPEN SCIENCE FRAMEWORK REGISTRATION https// osf.io/fhg94.

The COVID-19 pandemic disrupted graduate medical education, compelling training programs to abruptly transition to virtual educational formats despite minimal experience or proficiency. We surveyed residents from a national sample of internal medicine (IM) residency programs to describe their experiences with the transition to virtual morning report (MR), a highly valued core educational conference.

Assess resident views about virtual MR content and teaching strategies during the COVID-19 pandemic.

Anonymous, web-based survey.

Residents from 14 academically affiliated IM residency programs.

The 25-item survey on virtual MR included questions on demographics; frequency and reason for attending; opinions on who should attend and teach; how the virtual format affects the learning environment; how virtual MR compares to in-person MR with regard to participation, engagement, and overall education; and whether virtual MR should continue after in-person conferences can safely resume. The survey included a rt the integration of a virtual platform into the delivery of MR in the future.

Virtual MR was a valued alternative to traditional in-person MR during the COVID-19 pandemic. Residents feel that the virtual platform offers unique educational benefits independent of and in conjunction with in-person conferences. Residents support the integration of a virtual platform into the delivery of MR in the future.Despite enormous changes in medicine over the last 50 years, the oral presentation of newly admitted patients remains a core activity in academic teaching hospitals. With increased pace and complexity of care, it is time to refresh this tradition, as its efficiency and utility in contemporary practice are open to question. In this paper, we suggest a revised structure to help presenters organize their thoughts before the oral presentation and provide an online tool for doing so. We then offer tips on how to present the facts and inferences to the team in a compelling and memorable fashion; how to tell a story. Organizing information and oral presentation are advanced skills that require repeated practice to learn.

Engaging primary care providers (PCPs) in BRCA1/2 testing and results disclosure would increase testing access. The BRCA Founder OutReach (BFOR) study is a prospective study of BRCA1/2 founder mutation screening among individuals of Ashkenazi Jewish descent that sought to involve participants' PCPs in results disclosure. We used quantitative and qualitative methods to evaluate PCPs' perspectives, knowledge, and experience disclosing results in BFOR.

Among PCPs nominated by BFOR participants to disclose BRCA1/2 results, we assessed the proportion agreeing to disclose. To examine PCP's perspectives, knowledge, and willingness to disclose results, we surveyed 501 nominated PCPs. To examine PCPs' experiences disclosing results in BFOR, we surveyed 101 PCPs and conducted 10 semi-structured interviews.

In the BFOR study overall, PCPs agreed to disclose their patient's results 40.5% of the time. Two hundred thirty-four PCPs (46.7%) responded to the initial survey. Responding PCPs were more likely to agree to d17.

ClinicalTrials.gov (NCT03351803), November 24, 2017.

Improving accuracy of identification of COVID-19-related deaths is essential to public health surveillance and research. The verbal autopsy, an established strategy involving an interview with a decedent's caregiver or witness using a semi-structured questionnaire, may improve accurate counting of COVID-19-related deaths.

To develop and pilot-test the Verbal Autopsy Instrument for COVID-19 (VAIC) and a death adjudication protocol using it.

We used a multi-step process to design the VAIC and a protocol for its use. We developed a preliminary version of a verbal autopsy instrument specifically for COVID. We then pilot-tested this instrument by interviewing respondents about the deaths of 15 adults aged ≥65 during the initial COVID-19 surge in New York City. We modified it after the first 5 interviews. We then reviewed the VAIC and clinical information for the 15 deaths and developed a death adjudication process/algorithm to determine whether the underlying cause of death was definitely (40% of these pilot cases), probably (33%), possibly (13%), or unlikely/definitely not (13%) COVID-19-related. We noted differences between the adjudicated cause of death and a death certificate.

The VAIC and a death adjudication protocol using it may improve accuracy in identifying COVID-19-related deaths.

The VAIC and a death adjudication protocol using it may improve accuracy in identifying COVID-19-related deaths.

Hepatitis C virus (HCV) treatment has experienced a rapid transformation in the USA. New direct-acting antiviral (DAA) medications make treatment easier, less toxic, and more successful (90% or greater viral cure) than prior, interferon-based HCV medications. We sought to determine whether DAAs may have improved access to HCV treatment for hard-to-reach populations such as the homeless.

In a retrospective study of VA electronic medical record data, a cohort was created of 63,586 veterans with a positive HCV RNA or genotype test taken at any point from January 1, 2012, through December 31, 2016. Patient data were examined for up to 5 years using a discrete time survival model to assess the relationship between their housing status and receipt of HCV medications in 6-month time periods in both the interferon and DAA eras.

In the interferon era, the probability of HCV treatment in a given 6-month window among housed veterans, at 6.2% (95% CI 5.3-7.1%) was significantly higher than among veterans who were homeless or unstably housed; for example, among currently homeless veterans, the probability of treatment initiation, in a given 6-month window, was 2.6% (95% CI 1.9-3.3%). With the arrival of DAAs, each housing category had an increased probability of treatment initiation. For housed veterans, the probability was 8.6% (95% CI 8.3-8.9%) while for currently homeless veterans, it was 6.3% (95% CI 5.7-6.9%).

We found a clear indication that the likelihood of treatment initiation was greater for all veterans in the DAA era as compared to the interferon era. However, disparities in treatment initiation rates between housed and homeless veterans that were observed in the interferon era persisted in the DAA era.

We found a clear indication that the likelihood of treatment initiation was greater for all veterans in the DAA era as compared to the interferon era. However, disparities in treatment initiation rates between housed and homeless veterans that were observed in the interferon era persisted in the DAA era.

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