Publications by authors named "C Coyle"

268 Publications

The effectiveness of anti-inflammatory and anti-seizure medication for individuals with single enhancing lesion neurocysticercosis: A meta-analysis and expert group-based consensus recommendations.

PLoS Negl Trop Dis 2021 Mar 31;15(3):e0009193. Epub 2021 Mar 31.

Department of Neurology, Center for Global Health, School of Medicine, Technical University of Munich, Munich, Germany.

Single brain enhancing lesions (SEL) are the most common presentation of neurocysticercosis (NCC) observed on neuroimaging in people presenting with epileptic seizures not only on the Indian sub-continent and in travelers returning from cysticercosis-endemic regions, but also globally. The aim of this study, which consisted of a systematic review (CRD42019087665), a meta-analysis and an expert group consultation, was to reach consensus on the best anti-seizure medication and anti-inflammatory treatment for individuals with SEL NCC. Standard literature review methods were used, including the Cochrane risk of bias random effects model, meta-analyses were performed and the quality of the body of evidence was rated using GRADE tables. The expert committee included 12 gender and geographically balanced members and recommendations were reached by applying the GRADE framework for guideline development. The 1-1.5-year cumulative incidence of seizure recurrence, cyst resolution or calcification following anti-seizure medication (ASM) withdrawal was not statistically different between ASM of 6, 12 or 24 months. In contrast, in persons whose cyst calcified post treatment, longer ASM decreased seizure recurrence. The cumulative incidence ratio (CIR) 1-1.5 years after stopping ASM was 1.79 95% CI: (1.00, 3.20) for patients given 6 versus 24 months treatment. Duration of treatment had no effect on seizure recurrence in patients whose cyst did not calcify. Anti-inflammatory treatment with corticosteroids in patients treated with ASM compared to patients treated with ASM only showed a statistically significant beneficial effect on seizure reduction (CIR 0.44, 95% CI 0.23, 0.85) and cyst resolution (CIR 1.37, 95%CI: 1.07, 1.75). Our results indicate that ASM in patients with SEL NCC whose cysts resolved can be withdrawn, while patients whose cysts calcified seem to benefit from prolonged anti-seizure medication. Additional corticosteroid treatment was found to have a beneficial effect both on seizure reduction and cyst resolution.
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http://dx.doi.org/10.1371/journal.pntd.0009193DOI Listing
March 2021

The returned traveler with neurologic manifestations: could my patient have a parasite?

Curr Opin Infect Dis 2021 Mar 26. Epub 2021 Mar 26.

Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York, USA.

Purpose Of Review: The present review focuses on parasitic infections of the central nervous system (CNS) that can affect the international traveler.

Recent Findings: The epidemiology of imported parasitic infections is changing and clinicians are treating increasing numbers of returned travelers with parasitic infections in the CNS with which they are not familiar.

Summary: The epidemiology, life cycle, clinical manifestations, diagnosis, and treatment of parasites that affect the CNS will be discussed.
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http://dx.doi.org/10.1097/QCO.0000000000000732DOI Listing
March 2021

Saddle pulmonary embolism and clot in transit in COVID-19 infection: a case report of catastrophic venous thromboembolism.

Eur Heart J Case Rep 2020 Dec 7;4(6):1-6. Epub 2020 Dec 7.

Department of Medicine/Cardiology, New York City Health + Hospitals Corporation, Jacobi Medical Center 1400 Pelham Parkway, Bronx, NY 10461, USA.

Background : Coronavirus disease 2019 (COVID-19) is associated with a coagulopathy favouring thrombosis over bleeding that imparts a poor prognosis. Clot in transit (CIT) is considered a rare entity and the most severe form of venous thromboembolism (VTE), carrying a higher mortality than isolated pulmonary embolism (PE). The incidence of this phenomenon in patients with COVID-19 infection is unknown and likely under-recognized.

Case Summary : During the peak of the COVID-19 pandemic in New York City, a 70-year-old Hispanic female presented with syncope due to a saddle PE further complicated by a highly mobile CIT. Polymerase chain reaction was positive for COVID-19 infection, however, there was no evidence of lung parenchymal involvement or hyper-inflammation. Based on consensus from a multidisciplinary team, aspiration thrombectomy was attempted to treat this extreme case of VTE, however, the patient died during the procedure.

Discussion : This case raises awareness to the most catastrophic form of VTE, presenting in an early phase of COVID-19 infection without the typical hyper-inflammation and severe lung injury associated with development of COVID-related coagulopathy. It also serves to inform on the critical role echocardiography has in the comprehensive evaluation and re-evaluation of hospitalized patients with COVID-19, and the importance of a multidisciplinary organized approach in clinical decision-making for this complex and poorly understood disease and its sequelae.
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http://dx.doi.org/10.1093/ehjcr/ytaa437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891250PMC
December 2020

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

Eur Heart J 2021 Feb 18. Epub 2021 Feb 18.

Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK.

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.

Methods And Results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.
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http://dx.doi.org/10.1093/eurheartj/ehab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928984PMC
February 2021

Molecular coevolution of coagulation factor VIII and von Willebrand factor.

Blood Adv 2021 Feb;5(3):812-822

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Ancestral sequence reconstruction provides a unique platform for investigating the molecular evolution of single gene products and recently has shown success in engineering advanced biological therapeutics. To date, the coevolution of proteins within complexes and protein-protein interactions is mostly investigated in silico via proteomics and/or within single-celled systems. Herein, ancestral sequence reconstruction is used to investigate the molecular evolution of 2 proteins linked not only by stabilizing association in circulation but also by their independent roles within the primary and secondary hemostatic systems of mammals. Using sequence analysis and biochemical characterization of recombinant ancestral von Willebrand factor (VWF) and coagulation factor VIII (FVIII), we investigated the evolution of the essential macromolecular FVIII/VWF complex. Our data support the hypothesis that these coagulation proteins coevolved throughout mammalian diversification, maintaining strong binding affinities while modulating independent and distinct hemostatic activities in diverse lineages.
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http://dx.doi.org/10.1182/bloodadvances.2020002971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876868PMC
February 2021

Targeting the ectopy-triggering ganglionated plexuses without pulmonary vein isolation prevents atrial fibrillation.

J Cardiovasc Electrophysiol 2021 Feb 19;32(2):235-244. Epub 2021 Jan 19.

Myocardial Function Section, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Ganglionated plexuses (GPs) are implicated in atrial fibrillation (AF). Endocardial high-frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET-GP). The aim of this study was to understand the role of ET-GP ablation in the treatment of AF.

Methods: Patients with paroxysmal AF indicated for ablation were recruited. HFS mapping was performed globally around the left atrium to identify ET-GP. ET-GP was defined as atrial ectopy or atrial arrhythmia triggered by HFS. All ET-GP were ablated, and PVs were left electrically connected. Outcomes were compared with a control group receiving pulmonary vein isolation (PVI). Patients were followed-up for 12 months with multiple 48-h Holter ECGs. Primary endpoint was ≥30 s AF/atrial tachycardia in ECGs.

Results: In total, 67 patients were recruited and randomized to ET-GP ablation (n = 39) or PVI (n = 28). In the ET-GP ablation group, 103 ± 28 HFS sites were tested per patient, identifying 21 ± 10 (20%) GPs. ET-GP ablation used 23.3 ± 4.1 kWs total radiofrequency (RF) energy per patient, compared with 55.7 ± 22.7 kWs in PVI (p = <.0001). Duration of procedure was 3.7 ± 1.0 and 3.3 ± 0.7 h in ET-GP ablation group and PVI, respectively (p = .07). Follow-up at 12 months showed that 61% and 49% were free from ≥30 s of AF/AT with PVI and ET-GP ablation respectively (log-rank p = .27).

Conclusions: It is feasible to perform detailed global functional mapping with HFS and ablate ET-GP to prevent AF. This provides direct evidence that ET-GPs are part of the AF mechanism. The lower RF requirement implies that ET-GP targets the AF pathway more specifically.
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http://dx.doi.org/10.1111/jce.14870DOI Listing
February 2021

Immunomodulatory Therapy for the Management of Loiasis.

Clin Infect Dis 2020 Oct 24. Epub 2020 Oct 24.

Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New, York, USA.

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http://dx.doi.org/10.1093/cid/ciaa1367DOI Listing
October 2020

Learning in lockdown: preparing for the inaugural virtual conference of the International Society of Travel Medicine.

J Travel Med 2020 12;27(8)

Division of Infectious Diseases and Travel Medicine, Mount Auburn Hospital, Cambridge, MA, USA.

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http://dx.doi.org/10.1093/jtm/taaa220DOI Listing
December 2020

Housing with support for older people: a mixed-methods systematic review protocol.

HRB Open Res 2020 11;3:64. Epub 2020 Nov 11.

Health Research Board, Dublin, Ireland.

The implementation of housing with support is rapidly expanding, particularly as life expectancy is increasing throughout the world. This expansion is likely to intensify in the context of coronavirus disease 2019 (COVID-19), which has revealed the risks of relying primarily on nursing homes. This mixed-methods systematic review aims to: 1) explore older people's perceptions and experiences of housing with support and 2) examine the impact of providing housing with support for older people on their quality of life. The databases Ovid Medline, Ovid Social Policy & Practice, EBSCO CINAHL, and EBSCO SOCIndex will be searched, and grey literature will also be identified. Quality assessment will be carried out using Joanna Briggs Institute's Critical Appraisal Checklist for Qualitative Research as well as a tool from the National Institutes of Health for observational cohort studies. This review will employ convergent parallel design; as such, qualitative and quantitative findings will be synthesised separately in the initial stage of analysis. The results from the qualitative and quantitative syntheses will then be integrated in the final stage of the analysis. This systematic review will synthesise the evidence regarding older people's perceptions and experiences of housing with support and the impact of providing housing with support for older people on their quality of life.
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http://dx.doi.org/10.12688/hrbopenres.13124.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592024PMC
November 2020

The mental health and well-being benefits of exercise during the COVID-19 pandemic: a cross-sectional study of medical students and newly qualified doctors in the UK.

Ir J Med Sci 2020 Nov 4. Epub 2020 Nov 4.

Aberdeen University, Aberdeen, UK.

Background: University students have been uniquely affected by the COVID-19 pandemic. However, there is currently little data upon the measures that medical students and newly qualified doctors have taken to help their mental well-being and mood during the COVID-19 pandemic.

Aim: We aimed to identify the activities respondents found beneficial for their well-being and mental health and recorded a mood score from survey respondents.

Methods: A nationwide study was completed to investigate the mental health impact of the COVID-19 pandemic upon medical students and newly qualified doctors (interim foundation year one). We received 2075 respondents from across the UK.

Results: Physical activity was found to be the most common activity used by the survey respondents to help with their mental well-being (80.1%) (medical students, 83.7%; interim foundation doctors, 72.3%). Participants who stated that exercise helped their well-being had a mean score (SD) of 52.3 (20.7) which was significantly higher (P = 0.048) than those who reported that they did not exercise (49.8 (21.1)). Respondents who stated they had used exercise to help with their mental well-being had (on average) a higher mood score than those who did not. This was seen in both the medical student and interim foundation doctor subgroups.

Discussion: Exercise can help to benefit the well-being of medical students and interim foundation doctors. It is hoped that higher education providers and employers recognise the importance of promoting physical activity for the well-being of their students and staff, respectively.
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http://dx.doi.org/10.1007/s11845-020-02423-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641255PMC
November 2020

Cost Analysis of Emergency Department Criteria for Evaluation of Febrile Infants Ages 29 to 90 Days.

J Pediatr 2021 Apr 31;231:94-101.e2. Epub 2020 Oct 31.

Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH; Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH.

Objective: To compare the medical costs associated with risk stratification criteria used to evaluate febrile infants 29-90 days of age.

Study Design: A cost analysis study was conducted evaluating the Boston, Rochester, Philadelphia, Step-by-Step, and PECARN criteria. The percentage of infants considered low risk and rates of missed infections were obtained from published literature. Emergency department costs were estimated from the Centers for Medicare and Medicaid Services. The Health Care Cost and Utilization Project databases were used to estimate the number of infants ages 29-90 days presenting with fever annually and costs for admissions related to missed infections. A probabilistic Markov model with a Dirichlet prior was used to estimate the transition probability distributions for each outcome, and a gamma distribution was used to model costs. A Markov simulation estimated the distribution of expected annual costs per infant and total annual costs.

Results: For low-risk infants, the mean cost per infant for the criteria were Rochester: $1050 (IQR $1004-$1092), Philadelphia: $1416 (IQR, $1365-$1465), Boston: $1460 (IQR, $1411-$1506), Step-by-Step $942 (IQR, $899-$981), and PECARN $1004 (IQR, $956-$1050). An estimated 18 522 febrile 1- to 3-month-old infants present annually and estimated total mean costs for their care by criteria were: Rochester, $127.3 million (IQR, $126.1-$128.5); Philadelphia, $129.9 million (IQR, $128.7-$131.1); Boston, $128.7 million (IQR, $127.5-$129.9); Step-by-Step, $ 126.6 million (IQR, $125.4-$127.8); and PECARN, $125.8 million (IQR, $124.6-$127).

Conclusions: The Rochester, Step-by-step, and PECARN criteria are the least costly when evaluating infants 29-90 days of age with a fever.
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http://dx.doi.org/10.1016/j.jpeds.2020.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005434PMC
April 2021

Identifying and Managing Aqueous Film-Forming Foam-Derived Per- and Polyfluoroalkyl Substances in the Environment.

Environ Toxicol Chem 2021 Jan 9;40(1):24-36. Epub 2020 Dec 9.

Noblis, Chicago, Illinois, USA.

The use of aqueous film-forming foam (AFFF) has resulted in the widespread occurrence of per- and polyfluoroalkyl substances (PFAS) in groundwater, drinking water, soils, sediments, and receiving waters throughout the United States and other countries. We present the research and development efforts to date by the Strategic Environmental Research and Development Program (SERDP) and the Environmental Security Technology Certification Program (ESTCP) to measure PFAS in the environment, characterize AFFF-associated sources of PFAS, understand PFAS fate and behavior in the environment, assess the risk to ecological receptors, develop in situ and ex situ treatment technologies for groundwater, treat soils and investigation-derived wastes, and examine the ecotoxicity of PFAS-free fire suppression formulations. Environ Toxicol Chem 2021;40:24-36. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
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http://dx.doi.org/10.1002/etc.4894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839684PMC
January 2021

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.

BMJ Open 2020 10 5;10(10):e044566. Epub 2020 Oct 5.

Department of Medicine, University of Cambridge, Cambridge, UK

Objectives: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.

Design: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials.

Setting: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit.

Participants: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included.

Main Outcome Measures: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers.

Results: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials.

Conclusions: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.
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http://dx.doi.org/10.1136/bmjopen-2020-044566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536634PMC
October 2020

Tropical and travel-associated diseases.

Curr Opin Infect Dis 2020 10;33(5):333

Albert Einstein College of Medicine, Bronx, New York, USA.

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http://dx.doi.org/10.1097/QCO.0000000000000674DOI Listing
October 2020

Brain calcification because of neurocysticercosis: a vast field to be explored.

Curr Opin Infect Dis 2020 10;33(5):334-338

Albert Einstein College of Medicine, Bronx, New York, USA.

Purpose Of Review: Neurocysticercosis is the most common helminthic infection of the central nervous system caused by the larval stage of the pork tapeworm, Taenia solium. Endemic regions include Latin American countries, sub-Saharan Africa, and large regions of Asia, including the Indian subcontinent and is a global health problem. Seizures are the most common manifestation and approximately 30% of adult-onset seizures in endemic regions are attributable to NCC. Calcifications because of neurocysticercosis is the most common finding on imaging in endemic regions and are important seizure foci contributing to the burden of epilepsy.

Recent Findings: After treatment with antiparasitics for multiple viable parenchymal disease, approximately 38% of cysts that resolved after 6 months of therapy will result in residual calcifications, which represents a significant burden of residual disease. Calcified disease has been referred to as 'inactive disease', but there is accumulating evidence to suggest that calcified granulomas are actually dynamic and substantially contribute to the development and maintenance of seizures.

Summary: Calcified parenchymal neurocysticercosis contributes significantly to the development and maintenance of seizures in endemic regions. Understanding the pathogenesis of the role of calcified NCC in seizure development and risk factors for development of calcifications after treatment is critical to decreasing the burden of symptomatic disease in endemic regions.
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http://dx.doi.org/10.1097/QCO.0000000000000673DOI Listing
October 2020

US Department of Defense-Funded Research on Treatment of Per- and Polyfluoroalkyl Substance-Laden Materials.

Environ Toxicol Chem 2021 Jan 17;40(1):44-56. Epub 2020 Sep 17.

Science and Engineering for the Environment, Seattle, Washington, USA.

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http://dx.doi.org/10.1002/etc.4836DOI Listing
January 2021

New Insights into Calcified Neurocysticercosis: Closing the Knowledge Gap.

Clin Infect Dis 2020 Jul 3. Epub 2020 Jul 3.

Albert Einstein College of Medicine, Bronx, NY.

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http://dx.doi.org/10.1093/cid/ciaa927DOI Listing
July 2020

Editorial: simultaneous, prolonged monitoring of the acid pocket and oesophageal reflux. Authors' reply.

Aliment Pharmacol Ther 2020 07;52(2):398-399

School of Medical Sciences, Universiti Sains Malaysia, Kota Bahru, Malaysia.

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http://dx.doi.org/10.1111/apt.15835DOI Listing
July 2020

Letter to the editor: Unexpected high mortality in COVID-19 and diabetic ketoacidosis.

Metabolism 2020 09 24;110:154301. Epub 2020 Jun 24.

Division of Endocrinology, Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.metabol.2020.154301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311346PMC
September 2020

Duration of adhesion of swallowed alginates to distal oesophageal mucosa: implications for topical therapy of oesophageal diseases.

Aliment Pharmacol Ther 2020 08 16;52(3):442-448. Epub 2020 Jun 16.

Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Background: We have previously shown, ex vivo, that alginate solutions can have a topical protective effect on oesophageal mucosal biopsies exposed to simulated gastric juice. Oesophageal mucosal impedance can measure the duration of mucosal adherence of ionic solutions since the impedance drops when the solution is present, and rises to baseline as the solution clears.

Aim: To investigate the in vivo duration of adhesion of swallowed alginate solution to distal oesophageal mucosa.

Methods: We studied 20 healthy volunteers and 10 patients with heartburn. A pH-impedance catheter was inserted, and baseline distal channel oesophageal impedance measured. Healthy volunteers received 10 mL of either sodium alginate (Gaviscon Advance), Gaviscon placebo (no alginate) or viscous slurry (saline mixed with sucralose), given in a randomised, single-blinded order over three visits. Patients received either sodium alginate or placebo on two visits. Initial impedance drop was measured, then 1-minute mean impedance was measured each minute until ≥75% recovery to baseline.

Results: In healthy volunteers, sodium alginate adhered to the oesophageal mucosa for longer than placebo or viscous slurry (10.4 [8.7] minutes vs 1.1 [1.6] vs 3.6 [4.0], P < 0.01). In patients, sodium alginate adhered to the oesophageal mucosa for longer than placebo (9.0 (5.4) vs 3.7 (4.1), P < 0.01).

Conclusions: Sodium alginate solution adhered to the oesophageal mucosa for significantly longer than placebo or viscous slurry. This demonstrates that alginates could confer a protective benefit due to mucoadhesion and can be a basis for further development of topical protectants and for topical drug delivery in oesophageal disease.
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http://dx.doi.org/10.1111/apt.15884DOI Listing
August 2020

Chagas Disease in the New York City Metropolitan Area.

Open Forum Infect Dis 2020 May 6;7(5):ofaa156. Epub 2020 May 6.

Division of Infectious Diseases, Albert Einstein College of Medicine and Jacobi Medical Center, Bronx, New York, USA.

Background: Chagas disease, caused by the parasite , once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with However, awareness of Chagas disease among the medical community in the United States is poor.

Methods: We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment.

Results: The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation.

Conclusions: Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment.
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http://dx.doi.org/10.1093/ofid/ofaa156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255644PMC
May 2020

Randomised clinical trial: the effectiveness of Gaviscon Advance vs non-alginate antacid in suppression of acid pocket and post-prandial reflux in obese individuals after late-night supper.

Aliment Pharmacol Ther 2020 06 28;51(11):1014-1021. Epub 2020 Apr 28.

School of Medical Sciences, Universiti Sains Malaysia, Kota Bahru, Malaysia.

Background: Late-night supper increases the risk of postprandial reflux from the acid pocket especially in obesity. An alginate-based, raft-forming medication may be useful for obese patients with GERD.

Aims: To compare the efficacy of Gaviscon Advance (Reckitt Benckiser, UK) and a non-alginate antacid in post-supper suppression of the acid pocket and post-prandial reflux among obese participants.

Methods: Participants underwent 48 h wireless and probe-based pH-metry recording of the acid pocket and lower oesophagus, respectively, and were randomised to single post-supper (10 pm) dose of either Gaviscon Advance or a non-alginate antacid on the second night. Primary outcomes were suppression of median pH of acid pocket and lower oesophagus, measured every 10-minutes post-supper for 1 h. Secondary outcomes were suppression of % time pH < 4 at lower oesophagus and improvement in frequency and visual analogue score (VAS) of regurgitation.

Results: Of the 81 screened participants, 55 were excluded and 26 (mean age 33.5 years, males 77.8% and BMI 32.8 kg/m ) were randomised to Gaviscon Advance (n = 13) or antacid (n = 13). Median pH of the acid pocket but not the lower oesophagus was suppressed with Gaviscon Advance vs antacid (all P < 0.04) Gaviscon Advance but not antacid significantly reduced in % time pH < 4, symptom frequency and VAS on day 2 vs day 1 (all P < 0.05).

Conclusions: Among obese individuals, Gaviscon Advance was superior to a non-alginate antacid in post-supper suppression of the acid pocket. (Clinical trial registration unique identifier: NCT03516188).
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http://dx.doi.org/10.1111/apt.15746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318318PMC
June 2020

Clinically Meaningful Difference for the Infant Gastroesophageal Questionnaire Revised version (I-GERQ-R): A Quantitative Synthesis.

Patient Relat Outcome Meas 2020 6;11:87-93. Epub 2020 Mar 6.

Global Medical Affairs, Medical Affairs & Evidence Generation, Reckitt Benckiser, Slough, UK.

Background: Gastroesophageal reflux disease (GORD) is a common condition affecting 30% of infants aged 0-23 months. The Infant Gastroesophageal Questionnaire Revised version (I-GERQ-R) is an observer-reported outcome measures (ObsRO) developed to evaluate the impact of GORD on young infants. However, evidence regarding the clinically important difference (CID) for the I-GERQ-R is limited. The aim of this study was to determine a CID for the I-GERQ-R.

Methods: A literature review was undertaken (PsycInfo, Embase, MedLine and EconLit databases) for longitudinal studies involving the I-GERQ-R. Articles were not limited by language or publication date. A random effects model was applied to calculate an overall CID, along with I and Q statistics. Publication bias was also assessed.

Results: The search identified 42 articles; 11 were selected for full-text review and 7 articles were identified for full data extraction. The studies included a total of 661 infants (range: 30 to 313); 424 infants had been diagnosed with GORD (64%). The age range of the infants across the studies was from birth to 7 months. The overall CID was -6.54 (95% confidence interval: -4.35 to -8.74), Q = 17.96, p=0.08 and I=22.04.

Conclusion: This study derived a CID for the I-GERQ-R and indicated a threshold around 6 could signify a clinically important difference for this instrument. The lower limit of the 95% confidence interval suggested a threshold of 3 to 4 could represent a minimally important difference. These results may help inform clinical decisions in evaluating meaningful change in symptom severity in children affected by GORD.
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http://dx.doi.org/10.2147/PROM.S238673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068037PMC
March 2020

Barriers to malaria prevention among immigrant travelers in the United States who visit friends and relatives in sub-Saharan Africa: A cross-sectional, multi-setting survey of knowledge, attitudes, and practices.

PLoS One 2020 12;15(3):e0229565. Epub 2020 Mar 12.

Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America.

Background: Despite achievements in the reduction of malaria globally, imported malaria cases to the United States by returning international travelers continue to increase. Immigrants to the United States from sub-Saharan Africa (SSA) who then travel back to their homelands to visit friends and relatives (VFRs) experience a disproportionate burden of malaria illness. Various studies have explored barriers to malaria prevention among VFRs and non-VFRs-travelers to the same destinations with other purpose for travel-but few employed robust epidemiologic study designs or performed comparative analyses of these two groups. To better quantify the key barriers that VFRs face to implement effective malaria prevention measures, we conducted a comprehensive community-based, cross-sectional, survey to identify differences in malaria prevention knowledge, attitudes, and practices (KAP) among VFRs and others traveling to Africa and describe the differences between VFRs and other types of international travelers.

Methods And Findings: Three distinct populations of travelers with past or planned travel to malaria-endemic countries of SSA were surveyed: VFRs diagnosed with malaria as reported through a state health department; members of the general VFR population (community); and VFR and non-VFR travelers presenting to a travel health clinic, both before their pretravel consultation and again, after return from travel. A Community Advisory Board of African immigrants and prior qualitative research informed survey development and dissemination. Across the three groups, 489 travelers completed surveys: 351 VFRs and 138 non-VFRs. VFRs who reported taking antimalarials on their last trip rated their concern about malaria higher than those who did not. Having taken five or more trips to SSA was reported more commonly among VFRs diagnosed with malaria than community VFRs (44.0% versus 20.4%; p = 0.008). Among travel health clinic patients surveyed before and after travel, VFR travelers were less successful than non-VFRs in adhering to their planned use of antimalarials (82.2% versus 98.7%; p = 0.001) and employing mosquito bite avoidance techniques (e.g., using bed nets: 56.8% versus 81.8%; p = 0.009). VFRs who visited the travel health clinic were more likely than VFR respondents from the community to report taking an antimalarial (83.0% versus 61.9%; p = 0.009), or to report bite avoidance behaviors (e.g., staying indoors when mosquitoes were out: 80.9% versus 59.5%; p = 0.009).

Conclusions: We observed heterogeneity in malaria prevention behaviors among VFRs and between VFR and non-VFR traveler populations. Although VFRs attending the travel health clinic appear to demonstrate better adherence to malaria prevention measures than VFR counterparts surveyed in the community, specialized pretravel care is not sufficient to ensure chemoprophylaxis use and bite avoidance behaviors among VFRs. Even when seeking specialized pretravel care, VFRs experience greater barriers to the use of malaria prevention than non-VFRs. Addressing access to health care and upstream barrier reduction strategies that make intended prevention more achievable, affordable, easier, and resonant among VFRs may improve malaria prevention intervention effectiveness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229565PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067457PMC
June 2020

Comment on "Implementing a Psychiatry Clinic in a Student-Run Setting: a Medical Student Perspective".

Acad Psychiatry 2020 06 25;44(3):369-370. Epub 2020 Feb 25.

St George's, University of London, London, England.

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http://dx.doi.org/10.1007/s40596-020-01207-yDOI Listing
June 2020

Promoting Self-Advocacy Among Older Adults: Lessons From Boston's Senior Civic Academy.

J Appl Gerontol 2021 Apr 31;40(4):452-458. Epub 2020 Jan 31.

Age Strong Commission, City of Boston, MA, USA.

Fostering ways for older residents to be civically engaged is one dimension of an age-friendly community. While research on civic engagement among older adults often focuses on volunteering, this study focuses on advocacy and political involvement as another important form. The Age-Friendly Boston Initiative developed the Senior Civic Academy (SCA) program as a self-advocacy course that simultaneously educates older residents about policy-making processes and engages them in advocacy training to incorporate their voices in local policy and planning. This study details the formative evaluation of the SCA, and utilizes mixed methods to evaluate the program's impact on the participants ( = 49). Lessons learned from the SCA serve as a guide for other communities to develop programs that encourage civic engagement and advocacy among older adults.
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http://dx.doi.org/10.1177/0733464820902628DOI Listing
April 2021

Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus.

J Neuroendocrinol 2020 02 6;32(2):e12819. Epub 2020 Feb 6.

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.

The present study investigated neuroanatomically localised changes in de novo DNA methyltransferase expression in the female Siberian hamster (Phodopus sungorus). The objectives were to identify the neuroendocrine substrates that exhibit rhythmic Dnmt3a and Dnmt3b expression across the oestrous cycle and also examine the role of ovarian steroids. Hypothalamic Dnmt3a expression was observed to significantly increase during the transition from pro-oestrous to oestrous. A single bolus injection of diethylstilbestrol and progesterone was sufficient to increase Dnmt3a cell numbers and Dnmt3b immunoreactive intensity in the suprachiasmatic nucleus. In vitro analyses using an embryonic rodent cell line revealed that diethylstilbestrol was sufficient to induce Dnmt3b expression. Up-regulating DNA methylation in vitro reduced the expression of vasoactive intestinal polypeptide, Vip, and the circadian clock gene, Bmal1. Together, these data indicate that ovarian steroids drive de novo DNA methyltransferase expression in the mammalian suprachiasmatic nucleus and increased methylation may regulate genes involved in the circadian timing of oestrous: Vip and Bmal1. Overall, epigenetically mediated neuroendocrine reproductive events may reflect an evolutionarily ancient process involved in the timing of female fertility.
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http://dx.doi.org/10.1111/jne.12819DOI Listing
February 2020

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.

Lancet 2019 12 29;394(10214):2084-2095. Epub 2019 Nov 29.

University College London Cancer Institute, and University College London Hospitals, London, UK.

Background: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.

Methods: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3).

Findings: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m in group 1; 1233 mg/m in group 2; 1274 mg/m in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0-26·0] in group 1, 24·9 months [24·0-25·9] in group 2, 25·3 months [23·9-26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6-not reached] in group 1, 20·8 months [11·9-59·0] in group 2, 21·0 months [12·0-54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups.

Interpretation: Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations.

Funding: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.
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http://dx.doi.org/10.1016/S0140-6736(19)32259-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902268PMC
December 2019