Publications by authors named "Leslie C Hassett"

6 Publications

  • Page 1 of 1

Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review.

Therap Adv Gastroenterol 2021 24;14:1756284821993586. Epub 2021 Feb 24.

Department of Medicine and Physiology, Enteric NeuroScience Program, 200 First St SW, Rochester, MN 55905, USA.

Background And Aim: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life.

Methods: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both and studies were considered.

Results: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17-50%), IBS-D (37-62%) and IBS-C (4-25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies).

Conclusions: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.
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http://dx.doi.org/10.1177/1756284821993586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925957PMC
February 2021

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Risk of SARS-CoV-2 Infection or Hospitalization With COVID-19 Disease: A Systematic Review and Meta-Analysis.

Am J Ther 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Department of Medical Specialties, Infectious Diseases Section, King Fahad Medical City, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Swedish Heart and Vascular Institute, Swedish Medical Center, Seattle, WA; Department of Intensive Care, King Abdulaziz Medical City, King Saud bin Abdulaziz for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Houston Methodist DeBakey Heart and Vascular Center, Houston, TX; Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Mayo Clinic Libraries, Mayo Clinic, Rochester, MN; Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Poland; and Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Background: SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold.

Areas Of Uncertainty: These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease.

Data Sources: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020.

Therapeutic Advances: Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%.

Conclusion: Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.
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http://dx.doi.org/10.1097/MJT.0000000000001319DOI Listing
December 2020

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Mortality Among COVID-19 Patients: A Systematic Review and Meta-Analysis.

Am J Ther 2020 Nov 10. Epub 2020 Nov 10.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2).

Areas Of Uncertainty: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease.

Data Sources: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data.

Therapeutic Advances: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42-0.94) (I = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58-1.04) (I = 0%) and 0.97, 95% CI (0.73-1.30) (I = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis.

Conclusion: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.
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http://dx.doi.org/10.1097/MJT.0000000000001281DOI Listing
November 2020

Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis.

Thyroid 2020 Dec 29. Epub 2020 Dec 29.

Division of Endocrinology and Metabolism, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Levothyroxine (LT4) is one of the most commonly prescribed medications. Although considered a life-long replacement therapy, LT4 therapy can be discontinued for some patients. This study aims at: (i) reviewing the evidence on clinical outcomes of patients undergoing thyroid hormone replacement discontinuation, (ii) identifying the predictors of successful discontinuation, and (iii) systematically appraising frameworks used for deprescribing thyroid hormone. We searched multiple bibliographic databases, including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, from inception to February 2020 for studies in which thyroid hormone replacement was discontinued. Clinical outcomes assessed included: proportion of patients that remained euthyroid or needed to restart thyroid hormone replacement after discontinuation and frequency of clinical symptoms of hypothyroidism and adverse effects. We also evaluated predictors for discontinuation and deprescribing frameworks. Reviewers (F.J.K.T., N.B., N.M.S.O., S.M.) evaluated studies for inclusion, extracted data, and assessed methodological quality independently and in duplicate. Seventeen observational studies at moderate to high risk of bias met inclusion criteria, including a total of 1103 patients (86% women) with an age range of 2-81 years. Approximately a third of patients undergoing thyroid hormone discontinuation remained euthyroid at follow-up (37.2%, 95% confidence interval [CI 24.2-50.1%], I 97.5%). Subgroup analysis showed that patients with a previous diagnosis of overt hypothyroidism (OH) were less likely to remain euthyroid (11.8% [CI 0.4-23.2%], I 90.3%) than patients with a prior diagnosis of subclinical hypothyroidism (SCH) (35.6% [CI 8.2-62.9%], I 94.0%). No study followed a framework for systematically deprescribing LT4. Low-quality evidence suggests that up to a third of patients remained euthyroid after thyroid hormone discontinuation, with a higher proportion of patients with an initial diagnosis of SCH remaining euthyroid than patients with an initial diagnosis of OH. A deprescribing framework focusing on adequate selection of patients for deprescribing LT4 and a systematic process is warranted to guide clinicians in re-evaluating the need for LT4 in their patients.
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http://dx.doi.org/10.1089/thy.2020.0679DOI Listing
December 2020

Impact of air quality on the gastrointestinal microbiome: A review.

Environ Res 2020 07 7;186:109485. Epub 2020 Apr 7.

Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA; Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Electronic address:

Background: Poor air quality is increasingly associated with several gastrointestinal diseases suggesting a possible association between air quality and the human gut microbiome. However, details on this remain largely unexplored as current available research is scarce. The aim of this comprehensive rigorous review was to summarize the existing reports on the impact of indoor or outdoor airborne pollutants on the animal and human gut microbiome and to outline the challenges and suggestions to expand this field of research.

Methods And Results: A comprehensive search of several databases (inception to August 9, 2019, humans and animals, English language only) was designed and conducted by an experienced librarian to identify studies describing the impact of air pollution on the human gut microbiome. The retrieved articles were assessed independently by two reviewers. This process yielded six original research papers on the animal GI gastrointestinal microbiome and four on the human gut microbiome. β-diversity analyses from selected animal studies demonstrated a significantly different composition of the gut microbiota between control and exposed groups but changes in α-diversity were less uniform. No consistent findings in α or β-diversity were reported among the human studies. Changes in microbiota at the phylum level disclosed substantial discrepancies across animal and human studies.

Conclusions: A different composition of the gut microbiome, particularly in animal models, is associated with exposure to air pollution. Air pollution is associated with various taxa changes, which however do not follow a clear pattern. Future research using standardized methods are critical to replicate these initial findings and advance this emerging field.
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http://dx.doi.org/10.1016/j.envres.2020.109485DOI Listing
July 2020

The professional sabbatical: A systematic review and considerations for the health-system pharmacist.

Res Social Adm Pharm 2020 Dec 24;16(12):1632-1644. Epub 2020 Feb 24.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

Background: Sabbaticals are considered a professional development experience meant to foster growth and revitalize careers. The personal accounts of sabbaticals among medical professionals indicate high value from this experience. Benefits seen at the institutional and individual level include, but are not limited to, reduced burnout and increased job retention. Staffing issues, determining eligibility, and justifying time utilized may be just some barriers to implementing a sabbatical program accessible to the health-system pharmacist. In the literature, there is a dearth of information related to sabbaticals granted to the health-system pharmacist. However, many published experiences of nurses and physicians exist.

Objectives: A systematic review was performed to synthesize a qualitative yet evidence-based summary of information regarding sabbaticals. The primary aim of this review was to assess the reported benefits and prohibitive factors of taking a sabbatical as it may apply to the health-system pharmacist.

Methods: Three hundred twenty-eight English-language articles were identified through searching Ovid Medline, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and Scopus from database inception through December 6, 2019.

Results: A total of 172 articles consisting of studies, descriptions of institutional processes, individual accounts, editorials and letters to the editor, and review articles were included in this systematic review. Rejuvenation and new perspectives/skills to bring back to practice should be regarded as important benefits by institutional/departmental leadership as well as the benefits of reduced turnover and improved job satisfaction. Numerous barriers to completing a sabbatical can be overcome with proper planning.

Conclusion: This review provides limited insight into benefits and barriers to taking sabbaticals and serves as a basis for health-system pharmacy departments to consider initiating a program if one is not currently in place. Mini-sabbaticals may allow the health-system pharmacist to take a professional time away. Corollaries are drawn between a longitudinal pharmacy research award granted at Mayo Clinic - Rochester and ideas are provided for clinical or educational sabbaticals. It is clear that health-system pharmacy-specific information is lacking, and pharmacy department leadership should be encouraged to continue to share experiences of sabbaticals and outcomes.
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http://dx.doi.org/10.1016/j.sapharm.2020.02.011DOI Listing
December 2020