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To assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD) (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care.

Using UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016-2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups.

CMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (-0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups.

CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.

CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo-electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. selleck compound Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.

To evaluate how common echocardiographic metrics of aortic stenosis (AS) influence the proportion of patients who may be categorised as having severe stenosis and therefore considered for valve replacement.

Retrospective analysis was performed of all echocardiograms with aortic valve area (AVA) ≤1.2 cm

and peak jet velocity (V

) ≥3 m/s from 1 December 2014 through 30 October 2017 at a single academic medical centre. Echocardiographic indices collected include AVA, V

, left ventricular ejection fraction, stroke volume and annotated aortic stenosis severity.

Among 807 patients with AVA ≤1.2 cm

and V

≥3 m/s (44.0% female, median age 74 years (IQR 66-81)), 45.6% had V

≥4 m/s, while 75.8% had AVA ≤1 cm

. 40.0% of patients had concordant indices (V

≥4 m/s and AVA ≤1 cm

), and 35.8% had discordant indices (V

<4 m/s and AVA ≤1 cm

) of severe AS. Compared with those with concordant indices, patients with discordant indices were more commonly female (54.0% vs 44.3%, p<0.05) and less commonly characterised as severe (42.6% vs 93.8%, p<0.001). Patients with paradoxical low-flow, low-gradient severe AS by echocardiography were disproportionately female (61.5% vs 41.8%, p<0.001), and their disease was characterised as severe only 49.5% of the time.

Patients with discordant indices, who are disproportionately female, are commonly described in clinical echocardiography reports as having less than severe AS. link2 Given the potential benefit of AVR in patients with AVA ≤1 cm

regardless of V

, this could have important clinical implications.

Patients with discordant indices, who are disproportionately female, are commonly described in clinical echocardiography reports as having less than severe AS. Given the potential benefit of AVR in patients with AVA ≤1 cm2 regardless of Vmax, this could have important clinical implications.

Although required for healing, sleep is often disrupted during hospitalization. Blood pressure (BP) monitoring can be especially disruptive for pediatric inpatients and has few clinical indications. Our aim in this pilot study was to reduce unnecessary overnight BP monitoring and improve sleep for pediatric inpatients.

The intervention in June 2018 involved clinician education sessions and updated electronic health record (EHR) orders that enabled the forgoing of overnight BP checks. The postintervention period from July 2018 to May 2019 examined patient-caregiver surveys as outcome measures. link3 These surveys measured inpatient sleep and overnight disruptions and were adopted from validated surveys the Patient Sleep Questionnaire, expanded Brief Infant Sleep Questionnaire, and Potential Hospital Sleep Disruptions and Noises Questionnaire. Uptake of new sleep-friendly EHR orders was a process measure. Reported patient care escalations served as a balancing measure.

Interrupted time series analysis of EHR orders (n

= 493; n

= 1472) showed an increase in intercept for the proportion of patients forgoing overnight BP postintervention (+50.7%; 95% confidence interval 41.2% to 60.3%;

< .001) and a subsequent decrease in slope each week (-0.16%; 95% confidence interval -0.32% to -0.01%;

= .037). Statistical process control of surveys (n

= 263; n

= 131) showed a significant increase in sleep duration for patients older than 2, and nighttime disruptions by clinicians decreased by 19% (

< .001). Annual estimated cost savings were $15 842.01. No major adverse events in patients forgoing BP were reported.

A pilot study combining EHR changes and clinician education safely decreased overnight BP checks, increased pediatric inpatient sleep duration, and reduced nighttime disruptions by clinicians.

A pilot study combining EHR changes and clinician education safely decreased overnight BP checks, increased pediatric inpatient sleep duration, and reduced nighttime disruptions by clinicians.In rare circumstances, children who have suffered traumatic brain injury from child abuse are declared dead by neurologic criteria and are eligible to donate organs. When the parents are the suspected abusers, there can be confusion about who has the legal right to authorize organ donation. Furthermore, organ donation may interfere with the collection of forensic evidence that is necessary to evaluate the abuse. Under those circumstances, particularly in the context of a child homicide investigation, the goals of organ donation and collection and preservation of critical forensic evidence may seem mutually exclusive. In this Ethics Rounds, we discuss such a case and suggest ways to resolve the apparent conflicts between the desire to procure organs for donation and the need to thoroughly evaluate the evidence of abuse.

To test the effect of a 4-month telehealth home monitoring program (REACH), layered on usual care, on postdischarge outcomes in parents of infants recovering from cardiac surgery and their infants.

Randomized trial of infants discharged from the hospital after cardiac surgery for congenital heart disease. Consecutive infants with complex congenital heart disease undergoing cardiac surgery within 21 days of life were enrolled at 3 university-affiliated pediatric cardiac centers.

From 2012 to 2016, 219 parent-infant dyads were enrolled; 109 were randomly assigned to the intervention group and 110 to the control group. At 4 months postdischarge, parenting stress was not significantly different between groups (total Parenting Stress Index in the intervention group was 220 and in the control group was 215;

= .61). The percentages of parents who met posttraumatic stress disorder (PTSD) criteria and parent quality of life inventory scores were also not significantly different between the 2 groups (PTSD in tdmissions were common.

Although frameshift variants in the microsatellite area of shugoshin 1 (

) have been reported in the context of microsatellite instability-high (MSI-H)/deficient mismatch repair gastrointestinal cancer, most have been evaluated only in early stage I-III patients, and only two of its five microsatellite regions have been evaluated. Therefore, we investigated the frequency and MSI status of microsatellite frameshift variants in gastric cancer cases, including stage IV.

In a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software.

A frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delA

variant. However, c.973delA

variant was also observed in four cases of microsatellite stable.

Our study shows that

frameshift variants are not always associated with MSI status.

Our study shows that SGO1 frameshift variants are not always associated with MSI status.Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that the RNA-binding protein DDX5 binds to the mRNA transcripts of C3 and Fabp1 to augment their expressions posttranscriptionally. Knocking out DDX5 in epithelial cells protected mice from intestinal tumorigenesis and dextran sodium sulfate (DSS)-induced colitis. Identification of DDX5 as a common upstream regulator of tissue-specific oncogenic molecules provides an excellent therapeutic target for intestinal diseases.

To obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan.

We conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses.

We identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the 'business of Naswar', which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product.