Publications by authors named "G Neil Thomas"

5,364 Publications

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Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab141. Epub 2021 Oct 2.

University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: There is an urgent need for additional therapies to treat recurrent glioblastoma (GBM). Preclinical studies suggest that high dose macitentan, an oral dual endothelin receptor antagonist, enhances the cytotoxic effects of temozolomide (TMZ) in GBM, improving survival. This phase I trial investigated the maximum tolerated dose of macitentan combined with TMZ in patients with recurrent GBM and assessed the safety and tolerability of high dose macitentan in these patients (NCT01499251).

Methods: Adults with recurrent GBM received ascending doses of macitentan from 30 mg once daily concomitantly with TMZ. Safety and tolerability were assessed in addition to exploratory efficacy and pharmacokinetic endpoints. An ancillary study examined biomarker expression following macitentan treatment prior to surgical resection of recurrent GBM.

Results: Thirty-eight patients with recurrent GBM were administered macitentan doses up to 300 mg once daily; no dose-limiting toxicities were observed, and a maximum tolerated dose was not determined. All patients experienced at least one treatment-emergent adverse event (TEAE), the majority associated with GBM or TMZ treatment. TEAEs related to macitentan and TMZ were reported for 16 (42.1%) and 26 (68.4%) patients, respectively, with no serious macitentan-related TEAEs. Macitentan concentrations increased with dose, with no plateau in exposure. Substantial heterogeneity was observed in the expression of efficacy biomarkers within tumors. The Kaplan-Meier estimate of median overall survival across all dose groups was 9.4 (95% CI 8.5, 13.4) months.

Conclusion: High-dose macitentan was well tolerated in recurrent GBM patients concomitantly receiving TMZ. TEAEs were consistent with those seen in patients receiving either drug individually.
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http://dx.doi.org/10.1093/noajnl/vdab141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528265PMC
October 2021

Chronic Spontaneous Urticaria After COVID-19 Vaccine.

Cureus 2021 Sep 19;13(9):e18102. Epub 2021 Sep 19.

Allergy and Immunology, University of Maryland St. Joseph Medical Center, Towson, USA.

Public health efforts over the past few months have been aimed at vaccinating young adults. Moderna and Pfizer COVID-19 vaccines are widely available options. Cutaneous reactions to these vaccines have been described as self-limiting and relatively immediate after vaccine administration. In this case report, we present a young adult who received the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine and developed chronic, spontaneous urticaria.
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http://dx.doi.org/10.7759/cureus.18102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525834PMC
September 2021

A systematic review and meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from intervention studies aimed at improving glucose control.

Diabet Med 2021 Oct 22:e14730. Epub 2021 Oct 22.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK, B15 2TT.

Aims: Type 1 diabetes is characterised by the destruction of pancreatic beta cells. Significant levels of beta cells remain at diagnosis. Preserving these cells improves glucose control and protects from long-term complications. We undertook a systematic review and meta-analyses of all randomised controlled trials (RCTs) of interventions to preserve beta cell function in people newly diagnosed with type 1 diabetes. This paper reports the results of interventions for improving glucose control to assess whether they preserve beta cell function.

Methods: Searches for RCTs in MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and WHO International Clinical Trials Registry. Eligible studies included newly diagnosed type 1 diabetes patients, any intervention to improve glucose control and at least one month of follow-up. Data were extracted using a pre-defined data-extraction sheet with 10% of extractions checked by a second reviewer.

Results: Twenty-eight studies with 1,662 participants were grouped by intervention into six subgroups (alternative insulins, subcutaneous and intravenous insulin delivery, intensive therapy, glucose sensing, adjuncts). Only three studies demonstrated an improvement in glucose control as well as beta cell function. These interventions included intensive insulin therapy and use of an alternative insulin.

Conclusions: This is the largest comprehensive review of RCTs in this area. It demonstrates a lack of robust evidence that interventions to improve glucose control preserve beta cell function in new onset type 1 diabetes, although analysis was hampered by low quality evidence and inconsistent reporting of studies. Development of guidelines to support the design of trials in this field is a priority.
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http://dx.doi.org/10.1111/dme.14730DOI Listing
October 2021

Microbial Musings - September 2021.

Authors:
Gavin H Thomas

Microbiology (Reading) 2021 Oct;167(10)

Department of Biology, University of York, YO10 5YW, UK.

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http://dx.doi.org/10.1099/mic.0.001115DOI Listing
October 2021

Filling a gap in safety metrics: development of a patient-centred framework to identify and categorise patient-reported breakdowns related to the diagnostic process in ambulatory care.

BMJ Qual Saf 2021 Oct 16. Epub 2021 Oct 16.

Department of Medicine, University of Texas McGovern Medical School, Houston, Texas, USA.

Background: Patients and families are important contributors to the diagnostic team, but their perspectives are not reflected in current diagnostic measures. Patients/families can identify some breakdowns in the diagnostic process beyond the clinician's view. We aimed to develop a framework with patients/families to help organisations identify and categorise patient-reported diagnostic process-related breakdowns (PRDBs) to inform organisational learning.

Method: A multi-stakeholder advisory group including patients, families, clinicians, and experts in diagnostic error, patient engagement and safety, and user-centred design, co-developed a framework for PRDBs in ambulatory care. We tested the framework using standard qualitative analysis methods with two physicians and one patient coder, analysing 2165 patient-reported ambulatory errors in two large surveys representing 25 425 US respondents. We tested intercoder reliability of breakdown categorisation using the Gwet's AC1 and Cohen's kappa statistic. We considered agreement coefficients 0.61-0.8=good agreement and 0.81-1.00=excellent agreement.

Results: The framework describes 7 patient-reported breakdown categories (with 40 subcategories), 19 patient-identified contributing factors and 11 potential patient-reported impacts. Patients identified breakdowns in each step of the diagnostic process, including missing or inaccurate main concerns and symptoms; missing/outdated test results; and communication breakdowns such as not feeling heard or misalignment between patient and provider about symptoms, events, or their significance. The frequency of PRDBs was 6.4% in one dataset and 6.9% in the other. Intercoder reliability showed good-to-excellent reliability in each dataset: AC1 0.89 (95% CI 0.89 to 0.90) to 0.96 (95% CI 0.95 to 0.97); kappa 0.64 (95% CI 0.62, to 0.66) to 0.85 (95% CI 0.83 to 0.88).

Conclusions: The PRDB framework, developed in partnership with patients/families, can help organisations identify and reliably categorise PRDBs, including some that are invisible to clinicians; guide interventions to engage patients and families as diagnostic partners; and inform whole organisational learning.
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http://dx.doi.org/10.1136/bmjqs-2021-013672DOI Listing
October 2021
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