Publications by authors named "Catherine Smith"

389 Publications

Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.

MMWR Morb Mortal Wkly Rep 2021 Jul 23;70(29):1013-1019. Epub 2021 Jul 23.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15585/mmwr.mm7029a1DOI Listing
July 2021

Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

J Neurophysiol 2021 07 21. Epub 2021 Jul 21.

Department of Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States.

Intrapleural injection of cholera toxin B conjugated to saporin (CTB-SAP) mimics respiratory motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. 7d CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) primarily through TrkB and PI3K/Akt-dependent mechanisms (i.e., Gs-pathway, which can be initiated by adenosine 2A (A) receptors in naïve rats), while 28d CTB-SAP rats elicit moderate pLTF though BDNF and MEK/ERK-dependent mechanisms (i.e., Gq-pathway, which is typically initiated by serotonin (5-HT) receptors in naïve rats). Here, we tested the hypothesis that pLTF following CTB-SAP is: 1) A receptor-dependent at 7d; and 2) 5-HT receptor-dependent at 28d. Adult Sprague Dawley male rats were anesthetized, paralyzed, ventilated, and were exposed to acute intermittent hypoxia (AIH; 3, 5 min bouts of 10.5% O) following bilateral, intrapleural injections at 7d and 28d of: 1) CTB-SAP (25 μg), or 2) un-conjugated CTB and SAP (control). Intrathecal C delivery included either the: 1) A receptor antagonist (MSX-3; 10 μM; 12 μl); or 2) 5-HT receptor antagonist (methysergide; 20 mM; 15 μl). pLTF was abolished with A receptor inhibition in 7d, not 28d, CTB-SAP rats vs. controls (p<0.05), while pLTF was abolished following 5-HT receptor inhibition in 28d, not 7d, CTB-SAP rats vs. controls (p<0.05). Additionally, 5-HT receptor expression was unchanged in CTB-SAP rats vs. controls, while 5-HT receptor expression was decreased in CTB-SAP rats vs. controls (p<0.05). This study furthers our understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/jn.00236.2021DOI Listing
July 2021

The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study.

Lancet Rheumatol 2021 Jul 8. Epub 2021 Jul 8.

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.

Background: Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose.

Methods: In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination.

Findings: Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31-52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 [78%; 95% CI 67-87] of 77) than in controls (17 [100%; 80-100] of 17), with the lowest rate in those receiving methotrexate (seven [47%; 21-73] of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 [IQR 40-236]) than in controls (317 [213-487], p=0·0032), but was preserved in those receiving targeted biologics (269 [141-418]). Neutralising titres against the B.1.1.7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls.

Interpretation: Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness.

Funding: UK National Institute for Health Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2665-9913(21)00212-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266273PMC
July 2021

Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire?

Respirology 2021 Jul 5. Epub 2021 Jul 5.

School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Background And Objective: E-cigarette use has become increasingly prevalent, but there is some evidence demonstrating potential harms with frequent use. We aimed to identify the profiles of e-cigarette users from a regional community in Australia and investigate the associations of e-cigarettes with respiratory symptoms and lung function.

Methods: A total of 519 participants completed a cross-sectional study. Exposure to e-cigarettes was collected via a validated questionnaire. Respiratory symptoms were evaluated via a self-reported questionnaire and lung function measured with spirometry and forced oscillation technique (FOT). Linear and logistic regression models were fitted to investigate the associations between e-cigarettes and outcomes, while controlling for confounders such as tobacco smoking.

Results: Of the 519 participants, 46 (9%) reported e-cigarette use. Users tended to be younger (mean ± SD 45.2 ± 14.5 vs. 55.3 ± 16.0 years in non-users), concurrently using tobacco products (63% vs. 12% in non-users), have a mental health diagnosis (67% vs. 37% in non-users) and have self-reported asthma (63% vs. 42% in non-users). After controlling for known confounders, chest tightness (OR = 2.4, 95% CI 1.2-4.9, p = 0.02) was associated with e-cigarette use. Spirometry was not different after adjustment for confounding. However, FOT showed more negative reactance and a greater area under the reactance curve in e-cigarette users than non-users.

Conclusion: E-cigarette use was associated with increased asthma symptoms and abnormal lung mechanics in our sample, supporting a potential health risk posed by these products. Vulnerable populations such as young adults and those with mental health conditions have higher usage, while there is high concurrent tobacco smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/resp.14113DOI Listing
July 2021

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records.

JAC Antimicrob Resist 2021 Mar 4;3(1):dlab018. Epub 2021 Mar 4.

Institute of Health Informatics, University College London, London, UK.

Background: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians' prescribing. But much of the information needed could be sourced from electronic health records (EHRs).

Objectives: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records.

Methods: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017-August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (=61679 admissions).

Results: We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4-3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison.

Conclusions: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jacamr/dlab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210026PMC
March 2021

Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.

Clin Cancer Res 2021 Jul 8;27(14):4003-4011. Epub 2021 Jun 8.

Division of Hematology/Oncology, University of California, San Francisco, California.

Purpose: Biomarkers of response and resistance to FLT3 tyrosine kinase inhibitors (TKI) are still emerging, and optimal clinical combinations remain unclear. The purpose of this study is to identify co-occurring mutations that influence clinical response to the novel FLT3 inhibitor pexidartinib (PLX3397).

Experimental Design: We performed targeted sequencing of pretreatment blasts from 29 patients with internal tandem duplication (ITD) mutations treated on the phase I/II trial of pexidartinib in relapsed/refractory -ITD+ acute myeloid leukemia (AML). We sequenced 37 samples from 29 patients with available material, including 8 responders and 21 non-responders treated at or above the recommended phase II dose of 3,000 mg.

Results: Consistent with other studies, we identified mutations in , and a variety of epigenetic and transcriptional regulators only in non-responders. Among the most frequently mutated genes in non-responders was Cyclin D3 (. A total of 3 individual mutations in (Q276*, S264R, and T283A) were identified in 2 of 21 non-responders (one patient had both Q276* and S264R). No mutations were found in pexidartinib responders. Expression of the Q276* and T283A mutations in -ITD MV4;11 cells conferred resistance to apoptosis, decreased cell-cycle arrest, and increased proliferation in the presence of pexidartinib and other FLT3 inhibitors. Inhibition of CDK4/6 activity in mutant MV4;11 cells restored pexidartinib-induced cell-cycle arrest but not apoptosis.

Conclusions: Mutations in , a gene not commonly mutated in AML, are a novel cause of clinical primary resistance to FLT3 inhibitors in AML and may have sensitivity to CDK4/6 inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-3458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282743PMC
July 2021

A Systematic Review of New Approaches to Sexually Transmitted Infection Screening Framed in the Capability, Opportunity, Motivation, and Behavior Model of Implementation Science.

Sex Transm Dis 2021 Aug;48(8S):S58-S65

Lister Hill Library of Health Sciences.

Abstract: Chlamydia and gonorrhea are 2 of the most common bacterial sexually transmitted infections (STIs) worldwide. Rising chlamydia and gonorrhea rates along with increased closing of STI clinics has led many to seek STI testing in clinical settings such as urgent cares and walk-in clinics. However, with competing priorities, providing effective and efficient STI care can be difficult in these settings. This has left a growing need for the implementation of novel STI screening programs in other clinical settings. This review summarizes previous studies that have evaluated the clinical implementation of chlamydia and gonorrhea screening programs in these settings. Literature from January 2015 to February 2020 regarding the implementation or evaluation of STI screening programs in clinical settings was reviewed. Constructs from the Capability, Opportunity, Motivation, and Behavior model were used to organize results, as this model can aid in identifying specific strategies for behavior/process change interventions. We found that multiple STI screening programs have been implemented and evaluated in 5 different countries and multiple health care facilities including sexual health clinics, urgent cares, walk-in clinics, and university health clinics. When implementing new STI screening programs, sample-first, test-and-go services and molecular point-of-care (POC) testing approaches were found to be effective in increasing screening and reducing costs and time to treatment. At the health care systems level, these programs can help reduce STI screening costs and generate additional revenue for clinics. At the provider level, clear communication and guidance can help clinical and administrative staff in adopting new screening programs. Finally, at the patient level, new programs can reduce time to treatment and travel costs in visiting clinics multiple times for testing and treatment services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/OLQ.0000000000001461DOI Listing
August 2021

BedsideNotes: Sharing Physicians' Notes With Parents During Hospitalization.

Hosp Pediatr 2021 May 1;11(5):503-508. Epub 2021 Apr 1.

Department of Pediatrics, School of Medicine and Public Health,

Objectives: Physicians increasingly share ambulatory visit notes with patients to meet new federal requirements, and evidence suggests patient experiences improve without overburdening physicians. Whether sharing inpatient notes with parents of hospitalized children yields similar outcomes is unknown. In this pilot study, we evaluated parent and physician perceptions of sharing notes with parents during hospitalization.

Methods: Parents of children aged <12 years admitted to a hospitalist service at a tertiary children's hospital in April 2019 were offered real-time access to their child's admission and daily progress notes on a bedside inpatient portal (MyChart Bedside). Upon discharge, ambulatory OpenNotes survey items assessed parent and physician (attendings and interns) perceptions of note sharing.

Results: In all, 25 parents and their children's discharging attending and intern physicians participated. Parents agreed that the information in notes was useful and helped them remember their child's care plan (100%), prepare for rounds (96%), and feel in control (91%). Although many physicians (34%) expressed concern that notes would confuse parents, no parent reported that notes were confusing. Some physicians perceived that they spent more time writing and/or editing notes (28%) or that their job was more difficult (15%). Satisfaction with sharing was highest among parents (100%), followed by attendings (81%) and interns (35%).

Conclusions: Parents all valued having access to physicians' notes during their child's hospital stay; however, some physicians remained concerned about the potential negative consequences of sharing. Comparative effectiveness studies are needed to evaluate the effect of note sharing on outcomes for hospitalized children, families, and staff.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/hpeds.2020-005447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074112PMC
May 2021

Meeting Report: Psoriasis Stratification to Optimise Relevant Therapy Showcase.

J Invest Dermatol 2021 Mar 24. Epub 2021 Mar 24.

Centre for Dermatology Research, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom. Electronic address:

A stratified medicine approach for the treatment of psoriasis promises greater certainty of clinical decision making through prediction of response on the basis of clinical, pharmacological, and -omics data from an individual patient. As yet, there is no predictive model for treatment response in routine clinical use for psoriasis. The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium is a United Kingdom Medical Research Council‒funded, academic‒industrial stratified medicine consortium established with the objective of discovering the predictors and stratifiers of response of psoriasis to biologic therapies. A showcase meeting was convened and attended by 80 stakeholders at the Royal College of Physicians, London, United Kingdom on 18 November 2019. The purpose was to disseminate the research findings from the PSORT consortium discovered thus far. This report summarizes the presentations made on the day and the significant advances made by PSORT toward a stratified medicine approach to the management of psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2021.02.746DOI Listing
March 2021

Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia.

Nat Commun 2021 03 11;12(1):1583. Epub 2021 Mar 11.

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.

Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21810-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952600PMC
March 2021

Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.

Wellcome Open Res 2020 25;5:225. Epub 2021 Jan 25.

Centre of Public Health Data Science, Institute of Health Informatics, University College London, London, NW1 2DA, UK.

Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/wellcomeopenres.16304.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890379PMC
January 2021

Association of Patient Mental Health Status With the Level of Agreement Between Patient and Physician Ratings of Psoriasis Severity.

JAMA Dermatol 2021 Apr;157(4):413-420

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Importance: The emerging paradigm of treat-to-target in psoriasis requires accurate monitoring of treatment response. The commonly used physician global assessment tool does not capture the patient's perception of their disease. Patient assessments facilitate shared decision-making and foster patient-centered care; however, recent research reports a discordance between patient- and physician-reported psoriasis severity. Understanding the factors underlying this discordance may improve treatment satisfaction and disease outcomes.

Objectives: To evaluate the discordance between patient- and physician-reported measures of psoriasis severity and assess the association with patient mental health status.

Design, Setting, And Participants: A cohort study using repeated cross-sectional analysis of real-world longitudinal data was conducted at a large specialist psoriasis service serving London and Southeast England. A total of 502 patients attending the psoriasis service between May 12, 2016, and November 1, 2018, were included. Data analysis was conducted July 22 to October 22, 2019.

Main Outcomes And Measures: Psoriasis severity was assessed on each visit with identical 5-point physician and patient global assessment scales (clear/nearly clear, mild, moderate, severe, and very severe). Each patient completed validated self-report screens for depression and anxiety on each visit.

Results: Longitudinal data from 502 individuals with psoriasis (1985 total observations) were available. A total of 339 patients (68%) were men, 396 (79%) were White, mean (SD) age was 47 (13) years, and 197 patients (39%) had concurrent psoriatic arthritis, 43 (9%) screened positive for depression, and 49 (10%) screened positive for anxiety. There was discordance between physician and patient measures of disease severity in 768 of 1985 office appointments (39%); on 511 visits (26%) patients rated their psoriasis as less severe and on 257 visits (13%) patients rated their psoriasis as more severe compared with their physician. Individuals who screened positive for depression or anxiety were more likely to overestimate their psoriasis severity compared with their physician (relative risk ratio: depression, 2.7; 95% CI, 1.6-4.5; anxiety, 2.1; 95% CI, 1.3-3.4). These findings remained statistically significant after adjustment for age, ethnicity, sex, body mass index, smoking, number of comorbidities, treatment modality, and presence of psoriatic arthritis.

Conclusions And Relevance: The findings of this cohort study suggest that discordance between patient and physician assessments of psoriasis severity is associated with patients' mental health status. Recognition of anxiety and depression in individuals with psoriasis appears to be important when interpreting patient-reported outcome measures and informing appropriate treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2020.5844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931137PMC
April 2021

Outcomes Of Non-Cystic Fibrosis Related Bronchiectasis Post Lung Transplantation.

Intern Med J 2021 Mar 3. Epub 2021 Mar 3.

Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia.

Background: Lung transplantation is a recognised treatment for end-stage lung disease due to bronchiectasis. Non-CF bronchiectasis and CF are often combined into one cohort, however outcomes for non-CF bronchiectasis patients varies between centres, and in comparison to those for CF.

Aims: To compare lung transplantation mortality and morbidity of bronchiectasis (non-CF) patients to those with CF and other indications.

Methods: Retrospective analysis of patients undergoing lung transplantation between 01 January 2008-31 December 2013. Time to and cause of lung allograft loss was censored on 01 April 2018. A case-note review was conducted on a sub-group of 78 patients, to analyse hospital admissions as a marker of morbidity.

Results: 341 patients underwent lung transplantation, 22 (6%) had bronchiectasis compared to 69 (20%) with CF. The 5-year survival for the bronchiectasis group was 32%, compared to CF 69%, obstructive lung disease (OLD) 64%, pulmonary hypertension 62% and ILD 55% (p = 0.008). Lung allograft loss due to CLAD with predominant infection was significantly higher in the bronchiectasis group at 2 years. The rate of acute admissions was 2.24 higher in the bronchiectasis group when compared to OLD (p = 0.01). Patients with bronchiectasis spent 45.81 days in hospital per person year after transplantation compared with 18.21 days for CF.

Conclusions: Bronchiectasis patients in this study had a lower 5-year survival and poorer outcomes in comparison to other indications including CF. Bronchiectasis should be considered a separate entity to CF in survival analysis. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imj.15256DOI Listing
March 2021

Central venous pressure monitoring in critical care settings.

Br J Nurs 2021 Feb;30(4):230-236

Assistant Professor, Faculty of Health Studies, University of the Fraser Valley, Canada.

Patients who present with acute cardiovascular compromise require haemodynamic monitoring in a critical care unit. Central venous pressure (CVP) is the most frequently used measure to guide fluid resuscitation in critically ill patients. It is most often done via a central venous catheter (CVC) positioned in the right atrium or superior or inferior vena cava as close to the right atrium as possible. The CVC is inserted via the internal jugular vein, subclavian vein or via the femoral vein, depending on the patient and their condition. Complications of CVC placement can be serious, so its risks and benefits need to be considered. Alternative methods to CVC use include transpulmonary thermodilution and transoesophageal Doppler ultrasound. Despite its widespread use, CVP has been challenged in many studies, which have reported it to be a poor predictor of haemodynamic responsiveness. However, it is argued that CVP monitoring provides important physiologic information for the evaluation of haemodynamic instability. Nurses have central roles during catheter insertion and in CVP monitoring, as well as in managing these patients and assessing risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12968/bjon.2021.30.4.230DOI Listing
February 2021

The T681I mutation is highly resistant to imatinib and dasatinib and detectable in clinical samples prior to treatment.

Haematologica 2021 Feb 25. Epub 2021 Feb 25.

Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

Not available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2020.261354DOI Listing
February 2021

Ebola virus antibody decay-stimulation in a high proportion of survivors.

Nature 2021 02 27;590(7846):468-472. Epub 2021 Jan 27.

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-03146-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839293PMC
February 2021

Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England: results from the Bug Watch community cohort study.

BMC Infect Dis 2021 Jan 22;21(1):105. Epub 2021 Jan 22.

Institute of Health informatics, UCL, 222 Euston Road, London, NW1 2DA, UK.

Background: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye).

Methods: Bug Watch was an online prospective community cohort study of the general population in England (2018-2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity.

Results: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe.

Conclusions: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-05811-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820521PMC
January 2021

Bacteremia and Nodular Soft Tissue Infection in a Person Who Uses Tap Water to Inject Drugs.

Open Forum Infect Dis 2021 Jan 27;8(1):ofaa580. Epub 2020 Nov 27.

Section of Infectious Diseases, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

The ongoing North American epidemic of intravenous opioid and methamphetamine use increases the occurrence of bacteremia from environmental organisms. In this study, we report a case of bacteremia and associated nodular soft tissue infection in a person who uses tap water to inject drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793457PMC
January 2021

Mutations in Acute Myeloid Leukemia: Key Concepts and Emerging Controversies.

Front Oncol 2020 23;10:612880. Epub 2020 Dec 23.

Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, United States.

The FLT3 receptor is overexpressed on the majority of acute myeloid leukemia (AML) blasts. Mutations in are the most common genetic alteration in AML, identified in approximately one third of newly diagnosed patients. internal tandem duplication mutations (ITD) are associated with increased relapse and inferior overall survival. Multiple small molecule inhibitors of FLT3 signaling have been identified, two of which (midostaurin and gilteritinib) are currently approved in the United States, and many more of which are in clinical trials. Despite significant advances, resistance to FLT3 inhibitors through secondary mutations, upregulation of parallel pathways, and extracellular signaling remains an ongoing challenge. Novel therapeutic strategies to overcome resistance, including combining FLT3 inhibitors with other antileukemic agents, development of new FLT3 inhibitors, and FLT3-directed immunotherapy are in active clinical development. Multiple questions regarding mutated AML remain. In this review, we highlight several of the current most intriguing controversies in the field including the role of FLT3 inhibitors in maintenance therapy, the role of hematopoietic cell transplantation in mutated AML, use of FLT3 inhibitors in wild-type disease, significance of non-canonical mutations, and finally, emerging concerns regarding clonal evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.612880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787101PMC
December 2020

CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway.

J Invest Dermatol 2021 Jun 29;141(6):1553-1563.e3. Epub 2020 Dec 29.

AhRimmunity Lab, The Francis Crick Institute, London, United Kingdom; St John's Institute of Dermatology, King's College London, London, United Kingdom. Electronic address:

The AHR is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as a critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway downmodulates skin inflammatory responses in animal models and psoriasis clinical samples. In this study, we identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signaling in the context of skin inflammation. Mice constitutively expressing Cyp1a1 displayed increased CYP1A1 enzymatic activity in the skin, which resulted in exacerbated immune cell activation and skin pathology, mirroring that observed in Ahr-deficient mice. Inhibition of CYP1A1 enzymatic activity ameliorated the skin immunopathology by restoring beneficial AHR signaling. Importantly, patients with psoriasis displayed reduced activation of the AHR pathway and increased CYP1A1 enzymatic activity compared with healthy donors, suggesting that dysregulation of the AHR/CYP1A1 axis may play a role in inflammatory skin disease. Thus, modulation of CYP1A1 activity may represent a promising alternative strategy to harness the anti-inflammatory effect exerted by activation of the AHR pathway in the skin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152917PMC
June 2021

Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.

BMJ Open 2020 12 28;10(12):e038324. Epub 2020 Dec 28.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Introduction: Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods And Analysis: We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics And Dissemination: Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero Registration Number: CRD42020163941.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-038324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772326PMC
December 2020

Intact cord stabilisation and delivery room strategies: current practice in the UK.

Arch Dis Child Fetal Neonatal Ed 2020 Dec 28. Epub 2020 Dec 28.

Jessop Wing, Neonatal Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2020-321153DOI Listing
December 2020

Emergency department-based interventions affecting social determinants of health in the United States: A scoping review.

Acad Emerg Med 2021 06 2;28(6):666-674. Epub 2021 Feb 2.

Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Social determinants of health (SDoH) have significant implications for health outcomes in the United States. Emergency departments (EDs) function as the safety nets of the American health care system, caring for many vulnerable populations. ED-based interventions to assess social risk and mitigate social needs have been reported in the literature. However, the breadth and scope of these interventions have not been evaluated. As the field of social emergency medicine (SEM) expands, a mapping and categorization of previous interventions may help shape future research. We sought to identify, summarize, and characterize ED-based interventions aimed at mitigating negative SDoH.

Methods: We conducted a scoping review to identify and characterize peer-reviewed research articles that report ED-based interventions to address or impact SDoH in the United States. We designed and conducted a search in Medline, CINAHL, and Cochrane CENTRAL databases. Abstracts and, subsequently, full articles were reviewed independently by two reviewers to identify potentially relevant articles. Included articles were categorized by type of intervention and primary SDoH domain. Reported outcomes were also categorized by type and efficacy.

Results: A total of 10,856 abstracts were identified and reviewed, and 596 potentially relevant studies were identified. Full article review identified 135 articles for inclusion. These articles were further subdivided into three intervention types: a) provider educational intervention (18%), b) disease modification with SDoH focus (26%), and c) direct SDoH intervention (60%), with 4% including two "types." Articles were subsequently further grouped into seven SDoH domains: 1) access to care (33%), 2) discrimination/group disparities (7%), 3) exposure to violence/crime (34%), 4) food insecurity (2%), 5) housing issues/homelessness (3%), 6) language/literacy/health literacy (12%), 7) socioeconomic disparities/poverty (10%). The majority of articles reported that the intervention studied was effective for the primary outcome identified (78%).

Conclusion: Emergency department-based interventions that address seven different SDoH domains have been reported in the peer-reviewed literature over the past 30 years, utilizing a variety of approaches including provider education and direct and indirect focus on social risk and need. Characterization and understanding of previous interventions may help identify opportunities for future interventions as well as guide a SEM research agenda.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acem.14201DOI Listing
June 2021

Flexibility in individual funding schemes: How well did Australia's National Disability Insurance Scheme support remote learning for students with disability during COVID-19?

Soc Policy Adm 2020 Nov 25. Epub 2020 Nov 25.

Public Service Research Group, School of Business UNSW Canberra Canberra Australian Capital Territory Australia.

Individualized funding schemes are designed to offer people with disability greater choice and control over the services they receive. In this research, we report on a survey of over 700 families to explore how Australia's National Disability Insurance Scheme (NDIS) supported children and young people and their families to learn remotely during COVID-19. NDIS funding to support education during the first COVID-19 lockdown period forms an important case study of the flexibility of individualized funding schemes. Our results suggest that participant experiences varied widely, with some people able to make the changes they required and others left with a significant service gap. This shows that individual funding schemes are not necessarily more flexible than traditional systems in an emergency situation-useful flexibility depends on many factors, such as clarity of information giving, all actors having a shared message, proactive support of flexibility initiatives, and participants' ability to quickly navigate a complicated system. This research also highlights problems with the interface between the NDIS and mainstream services such as education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/spol.12670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753504PMC
November 2020

Hypersensitivity in patients receiving metal implants: a scoping review protocol.

JBI Evid Synth 2020 12 3;19(6):1404-1411. Epub 2020 Dec 3.

School of Nursing/Human and Social Development, University of Victoria, Victoria, BC, Canada.

Objective: The objective of this scoping review is to gather the available evidence on metal hypersensitivity to determine the extent of the problem and identify gaps in the evidence about screening practices.

Introduction: Hypersensitivity to metal was first reported in 1966. Since this time, the use of metal in prosthetic devices has increased with an associated rise in reported hypersensitivity reaction to other metals. Symptoms of metal hypersensitivity can be subtle, and it is unclear whether clinicians are aware of or routinely ask patients about metal hypersensitivity when documenting allergies. This can lead to a delay in diagnosis, which puts patients at risk of poor outcomes. Hence, there is a need to map the available evidence on hypersensitivity reaction in people who receive metallic device implantation.

Inclusion Criteria: The review will consider studies that include patients who undergo procedures involving metal implantation. The concept to be explored is hypersensitivity following a procedure that involves the implementation of a device with metal components. Implementation is defined as permanent integration of a foreign (non-biological) object into the human body to restore function.

Methods: The proposed scoping review will be conducted in accordance with JBI methodology for scoping reviews. Searches will be generated in multiple databases and updated as needed. Gray literature and organizational websites will also be searched. Titles, abstracts, and full articles will be screened according to the inclusion criteria. Studies published in English from 1960 to the present will be included. Data will be extracted and findings will be presented in tabular form with a narrative summary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11124/JBIES-20-00171DOI Listing
December 2020

Randomized Trial Replication Using Observational Data for Comparative Effectiveness of Secukinumab and Ustekinumab in Psoriasis: A Study From the British Association of Dermatologists Biologics and Immunomodulators Register.

JAMA Dermatol 2021 01;157(1):66-73

Centre for Dermatology Research, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester, United Kingdom.

Importance: Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies.

Objectives: To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated.

Design, Setting, And Participants: This comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed.

Main Outcomes And Measures: The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial.

Results: A total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses.

Conclusions And Relevance: This comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2020.4202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711562PMC
January 2021

Stakeholder Perspectives in Anticipation of Sharing Physicians' Notes With Parents of Hospitalized Children.

Acad Pediatr 2021 03 28;21(2):259-264. Epub 2020 Nov 28.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health (MM Kelly, CL Nacht, SM Dean, DJ Sklansky, MA Moreno, AS Thurber, and RJ Coller), Madison, Wis.

Objective: Elicit stakeholder perspectives on the anticipated benefits and challenges of sharing hospital physicians' admission and daily progress notes with parents at the bedside during their child's hospitalization and identify strategies to aid implementation of inpatient note sharing.

Methods: Five semistructured focus groups were conducted with 34 stakeholders (8 parents, 8 nurses, 5 residents, 7 hospitalists, 6 administrators) at a tertiary children's hospital from October to November 2018 to identify anticipated benefits, challenges, and implementation strategies prior to sharing inpatient physicians' notes. A facilitator guide elicited participants' perspectives about the idea of sharing notes with parents during their child's hospitalization. Three researchers used content analysis to analyze qualitative data inductively.

Results: Anticipated benefits of sharing inpatient notes included: Reinforcement of information, improved parental knowledge and empowerment, enhanced parent communication and partnership with providers, and increased provider accountability and documentation quality. Expected challenges included: Increased provider workload, heightened parental confusion, distress or anxiety, impaired parent relationship with providers, and compromised note quality and purpose. Suggested implementation strategies included: Setting staff and parent expectations upfront, providing tools to support parent education, and limiting shared note content and family eligibility.

Conclusions: Stakeholders anticipated multiple benefits and drawbacks of sharing notes with parents during their child's hospital stay and made practical suggestions for ways to implement inpatient note sharing to promote these benefits and mitigate challenges. Findings will inform the design and implementation of an intervention to share notes using an inpatient portal and evaluation of its effect on child, parent, and healthcare team outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acap.2020.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940595PMC
March 2021