Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions : A Mixed-Methods Cohort Study.

BACKGROUND: International guidelines recommend that primary care clinicians recognize obesity and offer treatment opportunistically, but there is little evidence on how clinicians can discuss weight and offer treatment in ways that are well received and effective. OBJECTIVE: To examine relationships between language used in the clinical visit and patient weight loss. DESIGN: Mixed-methods cohort study. SETTING: 38 primary care clinics in England participating in the Brief Intervention for Weight Loss trial. PARTICIPANTS: 246 patients with obesity seen by 87 general practitioners randomly sampled from the intervention group of the randomized clinical trial. MEASUREMENTS: Conversation analysis of recorded discussions between 246 patients with obesity and 87 clinicians regarding referral to a 12-week behavioral weight management program offered as part of the randomized clinical trial. Clinicians' interactional approaches were identified and their association with patient weight loss at 12 months (primary outcome) was examined. Secondary outcomes included patients' agreement to attend weight management, attendance, loss of 5% body weight, actions taken to lose weight, and postvisit satisfaction. RESULTS: Three interactional approaches were identified on the basis of clinicians' linguistic and paralinguistic practices: creating a sense of referrals as "good news" related to the opportunity of the referral (n = 62); "bad news," focusing on the harms of obesity (n = 82); or neutral (n = 102). Outcome data were missing from 57 participants, so weighted analyses were done to adjust for missingness. Relative to neutral news, good news was associated with increased agreement to attend the program (adjusted risk difference, 0.25 [95% CI, 0.15 to 0.35]), increased attendance (adjusted risk difference, 0.45 [CI, 0.34 to 0.56]), and weight change (adjusted difference, -3.60 [CI, -6.58 to -0.62]). There was no evidence of differences in mean weight change comparing bad and neutral news, and no evidence of differences in patient satisfaction across all 3 approaches. LIMITATIONS: Data were audio only, so body language and nonverbal cues could not be assessed. There is potential for selection bias and residual confounding. CONCLUSION: When raising the topic of excess weight in clinical visits, presenting weight loss treatment as a positive opportunity is associated with greater uptake of treatment and greater weight loss. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research School for Primary Care Research and the Foundation for the Sociology of Health and Illness.

Intercellular Adhesion Molecule 1 Functions as an Efferocytosis Receptor in Inflammatory Macrophages.

Intercellular adhesion molecule-1 (ICAM-1) is up-regulated during inflammation by several cell types. ICAM-1 is best known for its role in mediating leukocyte adhesion to endothelial cells and guiding leukocytes across the vascular wall. Recently, macrophages have been shown to express ICAM-1, however, their role in macrophage function is unclear. We found that ICAM-1 expression was induced during inflammatory macrophage polarization and high numbers of ICAM-1-expressing macrophages were noted in inflamed colon tissue in a murine colitis model and in human inflammatory bowel disease. Because tissue macrophages play a critical role in removing apoptotic/necrotic cells in inflammation and injury, a process termed efferocytosis, it was examined whether ICAM-1 contributes to this process. Genetic deletion (ICAM-1 knockout mice) or siRNA-mediated knockdown of ICAM-1 in isolated murine and human macrophages significantly impaired apoptotic cell (AC) engulfment. Impairment in the engulfment of Jurkat T cells, neutrophils, and epithelial cells was confirmed ex vivo by inflammatory macrophages and in vivo by thioglycolate-recruited peritoneal macrophages. Decreased efferocytosis was also seen in vitro and in vivo with inhibition of ICAM-1 adhesive interactions, using a function blocking anti-ICAM-1 antibody. Mechanistically, it was found that ICAM-1 actively redistributes to cluster around engulfed ACs to facilitate macrophage-AC binding. Our findings define a new role for ICAM-1 in promoting macrophage efferocytosis, a critical process in the resolution of inflammation and restoration of tissue homeostasis.

What Makes Opportunistic GP Interventions Effective? An Analysis of Behavior Change Techniques Used in 237 GP-Delivered Brief Interventions for Weight Loss.

BACKGROUND: Evidence shows that clinician-delivered brief opportunistic interventions are effective in obesity, and guidelines promote their use. However, there is no evidence on how clinicians should do this, and guidelines are not based on clinical evidence. PURPOSE: A trial (Brief Interventions for Weight Loss [BWeL]) showed that brief opportunistic interventions on obesity that endorsed, offered, and facilitated referral to community weight management service (CWMS) led to 77% agreeing to attend, and 40% attending CWMS, as well as significantly greater weight loss than control at 12 months. We assessed which behavior change techniques (BCTs) doctors used that were associated with CWMS attendance. METHODS: We coded 237 recorded BWeL interventions using the behavioral change techniques version one taxonomy. We also coded the BWeL training video to examine delivery of recommended BCTs. Mixed effects logistic regression assessed the association between each BCT, the total number of BCTs, and delivery of recommended BCTs, with patient's agreement to attend and actual CWMS attendance. RESULTS: Of 237 patients, 133 (56%) agreed to attend and 109 (46%) attended. Thirteen BCTs were used more than eight times but none of the 13 were associated with increased attendance. One, "practical social support," was significantly associated with increased patient agreement (odds ratio [OR] = 4.80, 95% confidence interval [CI] = 1.15, 20.13). Delivery of recommended BCTs and the total number of BCTs used were both associated with increased agreement (OR = 1.56, 95% CI = 1.09, 2.23 and OR = 1.34, 95% CI = 1.03, 1.75, respectively), but not attendance at CWMS (OR = 1.20, 95% CI = 0.98-1.47 and OR = 1.08, 95% CI = 0.94-1.24, respectively). CONCLUSIONS: There is no evidence that particular BCT can increase the effectiveness of brief opportunistic interventions for obesity in adults. However, using more BCTs and delivery of recommended BCTs may increase agreement to attend community weight management services.

Naltrexone-bupropion (Mysimba) in management of obesity: A systematic review and meta-analysis of unpublished clinical study reports.

AIMS: To compare the benefits and harms of naltrexone-bupropion using evidence from clinical study reports. METHODS: We searched Food and Drug Administration and European Medicines Agency websites, PubMed, and Clinicaltrials.gov (May 2016) to identify pivotal trials; we then sent a freedom of information request to the European Medicines Agency (July 2016). We included pivotal, phase III placebo-controlled trials. We assessed the risks of bias using the Cochrane criteria, and the quality of the evidence using GRADE. We used a random-effects model for meta-analyses. RESULTS: Over a 27-month period (July 2016 to August 2018), we received 31 batches of clinical study report documents containing over 65 000 pages of data from 4 pivotal trials (n = 4536). Significantly more participants who took naltrexone-bupropion achieved ≥5% reduction in body weight: risk ratio (RR) = 2.1 (95% confidence interval 1.35-3.28), P = .001, GRADE = low, number needed to treat (NNT) to benefit = 5 (3-17); this represents a 2.53 kg (1.85-3.21) reduction in baseline body weight compared with placebo. Naltrexone-bupropion had significantly beneficial effects on other cardiovascular risk factors; however, the true effect sizes for these are uncertain because of incomplete outcome data. Naltrexone-bupropion significantly increased the risk of adverse events: RR = 1.11 (1.05-1.18, P = .0004, GRADE = low, NNT to harm = 12 7-27); serious adverse events: RR = 1.70 (1.38-2.1, P < .00001, GRADE = moderate, NNT to harm = 21 13-38); and discontinuation because of adverse events: RR = 1.92 (1.65-2.24, P < .00001, GRADE = moderate, NNT to discontinue treatment = 9 8-13). CONCLUSIONS: Naltrexone-bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events. A rigorous process of postmarketing surveillance is required.

Effect of sensory attenuation on cortical movement-related oscillations.

This study examined the impact of induced sensory deficits on cortical, movement-related oscillations measured using electroencephalography (EEG). We hypothesized that EEG patterns in healthy subjects with induced sensory reduction would be comparable to EEG found after chronic loss of sensory feedback. EEG signals from 64 scalp locations were measured from 10 healthy subjects. Participants dorsiflexed their ankle after prolonged vibration of the tibialis anterior (TA). Beta band time frequency decompositions were calculated using wavelets and compared across conditions. Changes in patterns of movement-related brain activity were observed following attenuation of sensory feedback. A significant decrease in beta power of event-related synchronization was associated with simple ankle dorsiflexion after prolonged vibration of the TA. Attenuation of sensory feedback in young, healthy subjects led to a corresponding decrease in beta band synchronization. This temporary change in beta oscillations suggests that these modulations are a mechanism for sensorimotor integration. The loss of sensory feedback found in spinal cord injury patients contributes to changes in EEG signals underlying motor commands. Similar alterations in cortical signals in healthy subjects with reduced sensory feedback implies these changes reflect normal sensorimotor integration after reduced sensory input rather than brain plasticity. NEW & NOTEWORTHY Transient attenuation of sensory afferents in young, healthy adults led to similar changes in brain activity found previously in volunteers with incomplete spinal cord injury. Beta band power associated with ankle movement in these controls was attenuated after prolonged vibration of the tibialis anterior. Evoked potential measurements suggest that prolonged vibration reduces phasing across trials as the mechanism behind this attenuation of cortical activity.

Implications of Antibiotic Resistance for Patients' Recovery From Common Infections in the Community: A Systematic Review and Meta-analysis.

BACKGROUND: Antibiotic use is the main driver for carriage of antibiotic-resistant bacteria. The perception exists that failure of antibiotic treatment due to antibiotic resistance has little clinical impact in the community. METHODS: We searched MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science from inception to 15 April 2016 without language restriction. We included studies conducted in community settings that reported patient-level data on laboratory-confirmed infections (respiratory tract, urinary tract, skin or soft tissue), antibiotic resistance, and clinical outcomes. Our primary outcome was clinical response failure. Secondary outcomes were reconsultation, further antibiotic prescriptions, symptom duration, and symptom severity. Where possible, we calculated odds ratios with 95% confidence intervals by performing meta-analysis using random effects models. RESULTS: We included 26 studies (5659 participants). Clinical response failure was significantly more likely in participants with antibiotic-resistant Escherichia coli urinary tract infections (odds ratio [OR] = 4.19; 95% confidence interval [CI] = 3.27-5.37; n = 2432 participants), Streptococcus pneumoniae otitis media (OR = 2.51; 95% CI = 1.29-4.88; n = 921 participants), and S. pneumoniae community-acquired pneumonia (OR = 2.15; 95% CI = 1.32-3.51; n = 916 participants). Clinical heterogeneity precluded primary outcome meta-analysis for Staphylococcus aureus skin or soft-tissue infections. CONCLUSIONS: Antibiotic resistance significantly impacts on patients' illness burden in the community. Patients with laboratory-confirmed antibiotic-resistant urinary and respiratory-tract infections are more likely to experience delays in clinical recovery after treatment with antibiotics. A better grasp of the risk of antibiotic resistance on outcomes that matter to patients should inform more meaningful discussions between healthcare professionals and patients about antibiotic treatment for common infections.

Valid randomization-based p-values for partially post hoc subgroup analyses.

By 'partially post-hoc' subgroup analyses, we mean analyses that compare existing data from a randomized experiment-from which a subgroup specification is derived-to new, subgroup-only experimental data. We describe a motivating example in which partially post hoc subgroup analyses instigated statistical debate about a medical device's efficacy. We clarify the source of such analyses' invalidity and then propose a randomization-based approach for generating valid posterior predictive p-values for such partially post hoc subgroups. Lastly, we investigate the approach's operating characteristics in a simple illustrative setting through a series of simulations, showing that it can have desirable properties under both null and alternative hypotheses.

Assessing Risk and Preventing 30-Day Readmissions in Decompensated Heart Failure: Opportunity to Intervene?

Heart failure (HF) patients are at high risk of hospital readmission, which contributes to substantial health care costs. There is great interest in strategies to reduce rehospitalization for HF. However, many readmissions occur within 30 days of initial hospital discharge, presenting a challenge for interventions to be instituted in a short time frame. Potential strategies to reduce readmissions for HF can be classified into three different forms. First, patients who are at high risk of readmission can be identified even before their initial index hospital discharge. Second, ambulatory remote monitoring strategies may be instituted to identify early warning signs before acute decompensation of HF occurs. Finally, strategies may be employed in the emergency department to identify low-risk patients who may not need hospital readmission. If symptoms improve with initial therapy, low-risk patients could be referred to specialized, rapid outpatient follow-up care where investigations and therapy can occur in an outpatient setting.

Lessons for the next pandemic: analysis of the timing and outcomes including post-discharge decannulation rates for tracheostomy in severe COVID-19 respiratory failure.

PURPOSE: COVID-19 patients with respiratory failure frequently require prolonged ventilatory support that would typically warrant early tracheostomy. There has been significant debate on timing, outcomes, and safety of these procedures. The purpose of this study was to determine the epidemiological, hospital, and post-discharge outcomes of this cohort, based on early (ET) versus late (LT) tracheostomy. METHODS: Retrospective review (March 2020-January 2021) in a 5-hospital system of ventilated patients who underwent tracheostomy. Demographics, hospital/ICU length of stay (LOS), procedural characteristics, APACHE II scores at ICU admission, stabilization markers, and discharge outcomes were analyzed. Long-term decannulation rates were obtained from long-term acute care facility (LTAC) data. RESULTS: A total of 97 patients underwent tracheostomy (mean 61 years, 62% male, 64% Hispanic). Despite ET being frequently performed during active COVID infection (85% vs. 64%), there were no differences in complication types or rates versus LT. APACHE II scores at ICU admission were comparable for both groups; however, > 50% of LT patients met PEEP stability at tracheostomy. ET was associated with significantly shorter ICU and hospital LOS, ventilator days, and higher decannulation rates. Of the cohort discharged to an LTAC, 59% were ultimately decannulated, 36% were discharged home, and 41% were discharged to a skilled nursing facility. CONCLUSIONS: We report the first comprehensive analysis of ET and LT that includes LTAC outcomes and stabilization markers in relation to the tracheostomy. ET was associated with improved clinical outcomes and a short LOS, specifically on days of pre-tracheostomy ventilation and in-hospital decannulation rates.

To the point: Utility of laparoscopy for operative management of stabbing abdominal trauma.

BACKGROUND: Algorithms for managing penetrating abdominal trauma are conflicting or vague regarding the role of laparoscopy. We hypothesized that laparoscopy is underutilized among hemodynamically stable patients with abdominal stab wounds. METHODS: Trauma Quality Improvement Program data (2016-2019) were used to identify stable (SBP ≥110 and GCS ≥13) patients ≥16yrs with stab wounds and an abdominal procedure within 24hr of admission. Patients with a non-abdominal AIS ≥3 or missing outcome information were excluded. Patients were analyzed based on index procedure approach: open, therapeutic laparoscopy (LAP), or LAP-conversion to open (LCO). Center, clinical characteristics and outcomes were compared according to surgical approach and abdominal AIS using non-parametric analysis. RESULTS: 5984 patients met inclusion criteria with 7 â€‹% and 8 â€‹% receiving therapeutic LAP and LCO, respectively. The conversion rate for patients initially treated with LAP was 54 â€‹%. Compared to conversion or open, therapeutic LAP patients had better outcomes including shorter ICU and hospital stays and less infection complications, but were younger and less injured. Assessing by abdominal AIS eliminated ISS differences, meanwhile LAP patients still had shorter hospital stays. At time of admission, 45 â€‹% of open patients met criteria for initial LAP opportunity as indicated by comparable clinical presentation as therapeutic laparoscopy patients. CONCLUSIONS: In hemodynamically stable patients, laparoscopy remains infrequently utilized despite its increasing inclusion in current guidelines. Additional opportunity exists for therapeutic laparoscopy in trauma, which appears to be a viable alternative to open surgery for select injuries from abdominal stab wounds. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

GP delivered brief weight loss advice: associations between in-consultation behaviour change techniques and patient weight loss in recorded primary care discussions.

Background: Primary care clinicians are encouraged to intervene opportunistically, offering weight-loss advice to people living with obesity. The BWeL trial showed patients receiving brief weight-loss advice from their general practitioner lost weight at one year follow-up. We examined the behaviour change techniques (BCTs) clinicians used to identify which BCTs are associated with this weight loss. Methods: We coded 224 audio recorded interventions from the BWeL trial using the behavioural change techniques version one taxonomy (BCTTv1) and the 'refined taxonomy of behaviour change techniques to help people change their physical activity and healthy eating behaviours' (CALOR-RE taxonomy). Linear and logistic regressions were performed to analyse associations between behaviour change techniques used in these taxonomies and patient weight loss. Results: Mean intervention length was 86 s. We identified 28 different BCTs BCTTv1 and 22 from CALOR-RE. No BCTs or BCT domains were associated with mean weight loss at 12 months, loss of 5% bodyweight, or action taken at 3 months. The BCT 'Feedback on outcomes of behaviour (future)' was associated with an increased likelihood that the patient reported taking action to lose weight by 12 months (OR = 6.10, 95%CI = 1.20, 31.0). Conclusion: Although we found no evidence to support the use of particular BCTs, our results suggest that it is the brief intervention itself, rather than specific content, which may motivate weight loss. This can support clinicians to confidently intervene without needing complex training. Offering follow-up appointments can support positive changes to health behaviours, even if these are not associated with weight loss.

Validation of a miniaturized handheld arterial pressure monitor for guiding full and partial REBOA use during resuscitation.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-validated method for the control of noncompressible truncal hemorrhage. In lower resource or battlefield settings, the need for arterial line setup and monitoring is problematic and potentially prohibitive. We sought to evaluate the accuracy and precision of a miniaturized portable device (Centurion COMPASS®) versus standard arterial pressure monitoring using standard ER-REBOA and partial REBOA (pREBOA) as a high-fidelity and space-/time-conserving alternative. METHODS: A total of 40 swine underwent a four-phase validation/precision study (each phase using five ER-REBOAs and five pREBOAs). Phases I/II evaluated accuracy with full and pREBOA in uninjured animals. Phases III/IV duplicated the previous phases but in a severe hemorrhagic shock model. Carotid and femoral pressures were monitored with both intra-arterial pressure systems and the COMPASS® device. The vascular flow was measured by aortic flow probes. Correlation and Bland-Altman analysis were performed. RESULTS: There was a strong correlation in accuracy testing of proximal and distal COMPASS® devices compared to standard intra-arterial pressure monitoring (r = 0.94, 0.8; p < 0.005) as well as during precision testing (r = 0.98, 0.89 p < 0.005) in the uninjured phases. Similar accuracy and reliability were demonstrated in hemorrhagic shock, with a strong correlation for the proximal and distal COMPASS® devices (r = 0.98, 0.97; p < 0.005), as well as during precision testing (r = 0.99, 0.95; p < 0.005) in both full and pREBOA scenarios. Bland-Altman analysis showed extremely low bias between the COMPASS® and arterial line for both proximal (bias = 1.9) and distal (bias = 0.8) pressure measurements. CONCLUSION: The COMPASS® provides accurate and precise pressure measurements during standard and partial REBOA in both uninjured and shock conditions. This device may help extend and enhance capability in any low-resource/battlefield settings, or even eliminate the need for standard intra-arterial invasive pressure monitoring and external setup.

Tumor or Inflammatory Myofibroblastic Reaction in an Adolescent With an Abdominal Lymphatic Malformation?

We report the case of a 17-year-old male who presented with intractable nausea and vomiting. Cross-sectional imaging revealed a large retrogastric abdominal mass. Fine needle aspiration done via endoscopic ultrasound (EUS) was nondiagnostic. Exploratory laparotomy revealed a large inflammatory mass densely adherent to the stomach and retroperitoneum. Incisional biopsy frozen section revealed spindle cells, and subsequent resection of the mass with en-bloc subtotal gastrectomy with Roux-en-y gastrojejunostomy reconstruction was performed. Final pathology demonstrated a lymphatic malformation with reactive myofibroblastic proliferation. Inflammatory abdominal lymphatic malformations are especially rare and not well described in the literature. These masses may present diagnostic challenges until the specimen is sent for pathologic analysis.

Meta-Analysis of Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin According to Time in Therapeutic Range in Atrial Fibrillation.

Among atrial fibrillation (AF) patients, it is unclear whether the efficacy and safety of direct oral anticoagulants (DOAC) relative to warfarin is consistent across various levels of international normalized ratio (INR) control. To determine the efficacy and safety of DOAC agents compared with warfarin for patients with various levels of anticoagulation control as reflected by their time in therapeutic range (TTR), we conducted a systematic review and meta-analysis of published randomized controlled trials of DOAC versus (vs) warfarin which reported outcomes stratified by TTR. Based on reported center-based TTR (cTTR) ranges, degrees of INR control were categorized into 3 cTTR strata: low (<60%), intermediate (60% to 66%), and high (>66%). Pooled hazard ratios (HR) and 95% confidence intervals (CI) were determined for stroke or systemic embolism (SSE), major bleeding, and intracranial hemorrhage (ICH). Across all cTTR strata, DOAC-treated patients had lower risk of SSE versus warfarin, with a HR of 0.73 (95% CI 0.61 to 0.88) for the low, 0.76 (95% CI 0.59 to 0.98) intermediate; and 0.78 (95% CI 0.63 to 0.96) high cTTR subgroups. Compared with warfarin, DOAC-treated patients had lower risk of major bleeding in the low and intermediate cTTR strata, and similar risk in the highest cTTR stratum (HR 1.00, 95% CI 0.80 to 1.26). Patients treated with DOAC had lower risk of ICH compared with warfarin (HR 0.55, 95% CI; 0.40 to 0.74) which was observed across all cTTR strata. In conclusion, regardless of the degree of INR control, DOAC agents are preferable over warfarin as stroke prevention therapy for patients with AF.

Real-time bedside management and titration of partial resuscitative endovascular balloon occlusion of the aorta without an arterial line: Good for pressure, not for flow!

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) attempts to minimize ischemia/reperfusion injury while controlling hemorrhage. There are little data on optimal methods to evaluate and titrate partial flow, which typically requires invasive arterial line monitoring. We sought to examine the use of a miniaturized handheld digital pressure device (COMPASS; Mirador Biomedical, Seattle, WA) for pREBOA placement and titration of flow. METHODS: Ten swine underwent standardized hemorrhagic shock. Carotid and iliac pressures were monitored with both arterial line and COMPASS devices, and flow was monitored by aortic and superior mesenteric artery flow probes. Partial resuscitative endovascular balloon occlusion of the aorta was inflated to control hemorrhage for 15 minutes before being deflated to try targeting aortic flow of 0.7 L/min (using only the COMPASS device) by an operator blinded to the arterial line pressures and aortic flow. Correlations between COMPASS and proximal/distal arterial line were evaluated, as well as actual aortic flow. RESULTS: There was strong correlation between the distal mean arterial pressure (MAP) and the distal COMPASS MAP (r = 0.979, p < 0.01), as well as between the proximal arterial line and the proximal COMPASS on the pREBOA (r = 0.989, p < 0.01). There was a significant but weaker correlation between the distal compass MAP reading and aortic flow (r = 0.47, p < 0.0001), although it was not clinically significant and predicted flow was not achieved in a majority of the procedures. Of 10 pigs, survival times ranged from 10 to 120 minutes, with a mean survival of 50 minutes, and 1 pig surviving to 120 minutes. CONCLUSION: Highly reliable pressure monitoring is achieved proximally and distally without arterial lines using the COMPASS device on the pREBOA. Despite accurate readings, distal MAPs were a poor indicator of aortic flow, and titration based upon distal MAPs did not provide reliable results. Further investigation will be required to find a suitable proxy for targeting specific aortic flow levels using pREBOA.

Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes.

The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2'-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis.

The health impacts of preventive cardiovascular medication reduction on older populations: protocol for a systematic review and meta-analysis.

BACKGROUND: Polypharmacy is inevitable and appropriate for many conditions, but in some cases, it can be problematic resulting in an increased risk of harm and reduced quality of life. There has been an increasing interest to reduce cardioprotective medications in older adults to potentially reduce the risk of harm due to treatment; however, there is no evidence on safety and efficacy to support this practice currently. This paper describes a protocol for a systematic review on the safety and efficacy of reducing cardioprotective medication in older populations. METHODS: MEDLINE (PubMed), Embase (Ovid), and CENTRAL (Cochrane Central Register of Controlled Trials) will be searched from their inception onwards for relevant studies. Randomised controlled trials and non-randomised studies on interventions (prospective, retrospective cohort, case-control) conducted in older adults (75 years or older) examining reduction of cardioprotective medications will be included. The primary outcome of this study will be all-cause hospitalisation. Secondary outcome variables of interest are all-cause hospitalisation, mortality, quality of life, serious adverse events, major adverse cardiovascular events, falls, fractures, cognitive functioning, bleeding events, renal functioning, medication burden, drug reinstatement, time-in-hospital, and frailty status. Two reviewers will independently screen all citations, full-text articles, and extract data. Confidence in cumulative evidence will be assessed using the GRADE approach; the risk of bias will be assessed by the RoB-II tool for randomised controlled studies and ROBINS-I for non-randomised studies. Where sufficient data are available, we will conduct a random effects meta-analysis by combining the outcomes of the included studies. Sub-group analysis and meta-regression are planned to assess the potential harms and risks of different drug classes and the impacts in different patient populations (e.g. sex, cognitive status, renal status, and age). DISCUSSION: The study will be a comprehensive review on all published articles identified using our search strategy on the safety and efficacy of cardioprotective medication reduction in the older population. The findings will be crucial to inform clinicians on potential health outcomes of reducing cardiovascular medication in the elderly. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020208223.

Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: a qualitative study of university students and staff.

OBJECTIVES: Successful implementation of asymptomatic testing programmes using lateral flow tests (LFTs) depends on several factors, including feasibility, acceptability and how people act on test results. We aimed to examine experiences of university students and staff of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. DESIGN AND SETTING: A qualitative study using semistructured remote interviews and qualitative survey responses, which were analysed thematically. PARTICIPANTS: People who were participating in weekly testing feasibility study, between October 2020 and January 2021, at the University of Oxford. RESULTS: We interviewed 18 and surveyed 214 participants. Participants were motivated to regularly self-test as they wanted to know whether or not they were infected with SARS-CoV-2. Most reported that a negative test result did not change their behaviour, but it did provide them with reassurance to engage with permitted activities. In contrast, some participants reported making decisions about visiting other people because they felt reassured by a negative test result. Participants valued the training but some still doubted their ability to carry out the test. Participants were concerned about safety of attending test sites with lots of people and reported home testing was most convenient. CONCLUSIONS: Clear messages highlighting the benefits of regular testing for family, friends and society in identifying asymptomatic cases are needed. This should be coupled with transparent communication about the accuracy of LFTs and how to act on either a positive or negative result. Concerns about safety, convenience of testing and ability to do tests need to be addressed to ensure successful scaling up of asymptomatic testing.

Is cerebral perfusion maintained during full and partial resuscitative endovascular balloon occlusion of the aorta in hemorrhagic shock conditions?

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is a technology that occludes aortic flow and allows for controlled deflation and restoration of varying distal perfusion. Carotid flow rates (CFRs) during partial deflation are unknown. Our aim was to measure CFR with the different pREBOA balloon volumes and correlate those to the proximal mean arterial pressure (PMAP) and a handheld pressure monitoring device (COMPASS; Mirador Biomedical, Seattle, WA). METHODS: Ten swine underwent a hemorrhagic injury model with carotid and iliac arterial pressures monitored via arterial lines. Carotid and aortic flow rates were monitored with Doppler flow probes. A COMPASS was placed to monitor proximal pressure. The pREBOA was inflated for 15 minutes then partially deflated for an aortic flow rate of 0.7 L/min for 45 minutes. It was then completely deflated. Proximal mean arterial pressures and CFR were measured, and correlation was evaluated. Correlation between CRF and COMPASS measurements was evaluated. RESULTS: Carotid flow rate increased 240% with full inflation. Carotid flow rate was maintained at 100% to 150% of baseline across a wide range of partial deflation. After full deflation, CFR transiently decreased to 45% to 95% of baseline. There was strong positive correlation (r > 0.85) between CFR and PMAP after full inflation, and positive correlation with partial inflation (r > 0.7). Carotid flow rate had strong correlation with the COMPASS with full REBOA (r > 0.85) and positive correlation with pREBOA (r > 0.65). CONCLUSION: Carotid flow rate is increased in a hemorrhagic model during full and partial inflation of the pREBOA and correlates well with PMAP. Carotid perfusion appears maintained across a wide range of pREBOA deflation and could be readily monitored with a handheld portable COMPASS device instead of a standard arterial line setup.