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Article ; Online: Does metformin affect outcomes in COVID-19 patients with new or pre-existing diabetes mellitus? A systematic review and meta-analysis.

Ganesh, Adithan / Randall, Michael D

British journal of clinical pharmacology

2022 Volume 88, Issue 6, Page(s) 2642–2656

Abstract: Aims: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in ... ...

Abstract	Aims: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM. Methods: Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842. Results: In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I Conclusion: Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.
MeSH term(s)	Bias ; COVID-19/drug therapy ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/epidemiology ; Humans ; Metformin/therapeutic use ; Pandemics
Chemical Substances	Metformin (9100L32L2N)
Language	English
Publishing date	2022-02-23
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15258
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Article: Antimicrobial usage in broiler chicken production in the United States, 2013-2021.

Singer, Randall S / Schrag, Nora F D / Ricke, Isabel / Apley, Michael D

Frontiers in veterinary science

2023 Volume 10, Page(s) 1139908

Abstract: Although efforts to improve antimicrobial stewardship should include the collection of antimicrobial use data, most antimicrobial datasets collected at the national level consist of antimicrobial sales data which cannot inform stewardship. These data ... ...

Abstract	Although efforts to improve antimicrobial stewardship should include the collection of antimicrobial use data, most antimicrobial datasets collected at the national level consist of antimicrobial sales data which cannot inform stewardship. These data lack context, such as information regarding target species, disease indication, and regimen specifics like dose, route and duration. Therefore, the goal of this study was to develop a system for collecting data on the use of antimicrobials in the U.S. broiler chicken industry. This study utilized a public-private partnership to enable collection and protection of sensitive data from an extremely large industry while releasing deidentified and aggregated information regarding the details of antimicrobial use on U.S. broiler chicken farms over time. Participation was voluntary. Data were collected for the period 2013 through 2021 and are reported on a calendar year basis. Using production statistics from USDA:NASS as a denominator, the data supplied by participating companies represented approximately 82.1% of broiler chicken production in the U.S. in 2013, approximately 88.6% in 2017, and approximately 85.0% in 2021. The data that were submitted for 2021 are based on approximately 7,826,121,178 chickens slaughtered and 50,550,817,859 pounds liveweight produced. Granular flock-level treatment records were available for 75-90% of the birds represented in the 2018-2021 dataset. There was no use of antimicrobials in the hatchery for the years 2020 and 2021. Medically important in-feed antimicrobial use decreased substantially, with all in-feed tetracycline use being eliminated by 2020, and the use of virginiamycin being reduced by more than 97% since 2013. Medically important water-soluble antimicrobials are used for the treatment of disease in broiler production. Use decreased substantially for most water-soluble antimicrobials. The most important diseases necessitating treatment were necrotic enteritis and gangrenous dermatitis as well as
Language	English
Publishing date	2023-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1139908
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Article: On-farm antimicrobial usage in commercial turkey production in the United States, 2013-2021.

Singer, Randall S / Schrag, Nora F D / Ricke, Isabel / Apley, Michael D

Frontiers in veterinary science

2023 Volume 10, Page(s) 1158943

Abstract: A key component of antimicrobial stewardship is the ability to collect antimicrobial use data and ultimately use this information to ensure that administrations are necessary and effective. National antimicrobial sales data cannot help in this capacity ... ...

Abstract	A key component of antimicrobial stewardship is the ability to collect antimicrobial use data and ultimately use this information to ensure that administrations are necessary and effective. National antimicrobial sales data cannot help in this capacity because the data lack context, for example, details concerning target species and disease indication. The objective of this study was to continue the development of a system for collecting flock-level on-farm antimicrobial use data from the U.S. turkey industry and to have it be representative of national turkey production in the U.S. This study utilized a public-private partnership to enable collection and protection of sensitive flock-level data from an extremely large industry while releasing deidentified and aggregated information regarding the details of antimicrobial use on U.S. turkey farms over time. Participation was voluntary. Data were collected for the period 2013 through 2021 and are reported on a calendar year basis. Using production statistics from USDA:NASS as a denominator, the data supplied by participating companies represented approximately 67.3% of turkey production in the U.S. in 2013, approximately 69.1% in 2017, and approximately 71.4% in 2021. The data that were submitted for 2021 are based on approximately 149,000,192 turkeys slaughtered and 4,929,773,506 pounds liveweight produced. Detailed prescription records representing approximately 60-70% of the birds were available for the 2018-2021 dataset. The estimated percentage of turkey poults placed that received hatchery antimicrobials decreased from 96.9% in 2013 to 40.5% in 2021. The use of in-feed antimicrobials was practically eliminated, with in-feed tetracycline being the only medically important antimicrobial used in 2021. Use of in-feed tetracyclines decreased approximately 80% between 2013 and 2021. Water-soluble antimicrobial use declined over the study period. Between 2013 and 2021, water-soluble penicillin use decreased approximately 41% but water-soluble tetracycline use increased approximately 22%. Key diseases that were treated with water-soluble antimicrobials included bacterial poult enteritis and clostridial dermatitis. Efforts to reduce the incidence of these diseases would reduce the need for antimicrobial therapy, thereby enabling continued decreases in antimicrobial use without sacrificing animal welfare. However, this will require an investment in research to find efficacious and cost-effective mitigation strategies.
Language	English
Publishing date	2023-06-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1158943
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Article ; Online: Demographic, behavioral, dietary, and clinical predictors of high-sensitivity C-reactive protein: The National Health and Nutrition Examination Surveys (NHANES).

Randall, Zachary D / Brouillard, Adam M / Deych, Elena / Rich, Michael W

American heart journal plus : cardiology research and practice

2022 Volume 21, Page(s) 100196

Abstract: Aims: High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is associated with atherosclerosis, and recent studies indicate that therapies targeting inflammation are associated with reductions in cardiovascular risk. However, factors ... ...

Abstract	Aims: High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is associated with atherosclerosis, and recent studies indicate that therapies targeting inflammation are associated with reductions in cardiovascular risk. However, factors predictive of elevated hs-CRP in the general population have not been elucidated. Methods: In this cross-sectional study, multivariable logistic regression analysis was used to identify independent predictors of elevated hs-CRP (≥3 mg/L) utilizing the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle. The model was verified using the independent NHANES 2017-2018 cycle. Candidate variables comprised demographic, behavioral, dietary, and clinical factors. The study included 5412 adults from the 2015-2016 cohort and 5856 adults from the 2017-2018 cohort. Results: Significant independent predictors of elevated hs-CRP included: older age (OR 1.09 per decade; 95 % CI 1.03-1.14; P = 0.024), female sex (OR 1.57; 95 % CI 1.36-1.80; P = 0.003), Black vs White race (OR 1.31; 95 % CI 1.10-1.56; P = 0.037), increased BMI (OR 1.12 per kg/m Conclusion: Older age, female sex, Black race, increased BMI, higher white blood cell count, and self-reported poor health were independent predictors of elevated hs-CRP levels. Additional studies are needed to determine if behavioral modifications can lower hs-CRP and whether this translates to reduced risk for cardiovascular disease and other conditions associated with chronic inflammation.
Language	English
Publishing date	2022-08-27
Publishing country	United States
Document type	Journal Article
ISSN	2666-6022
ISSN (online)	2666-6022
DOI	10.1016/j.ahjo.2022.100196
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Article ; Online: Antimicrobial usage in broiler chicken production in the United States, 2013–2021

Randall S. Singer / Nora F. D. Schrag / Isabel Ricke / Michael D. Apley

Frontiers in Veterinary Science, Vol

2023 Volume 10

Abstract	Although efforts to improve antimicrobial stewardship should include the collection of antimicrobial use data, most antimicrobial datasets collected at the national level consist of antimicrobial sales data which cannot inform stewardship. These data lack context, such as information regarding target species, disease indication, and regimen specifics like dose, route and duration. Therefore, the goal of this study was to develop a system for collecting data on the use of antimicrobials in the U.S. broiler chicken industry. This study utilized a public-private partnership to enable collection and protection of sensitive data from an extremely large industry while releasing deidentified and aggregated information regarding the details of antimicrobial use on U.S. broiler chicken farms over time. Participation was voluntary. Data were collected for the period 2013 through 2021 and are reported on a calendar year basis. Using production statistics from USDA:NASS as a denominator, the data supplied by participating companies represented approximately 82.1% of broiler chicken production in the U.S. in 2013, approximately 88.6% in 2017, and approximately 85.0% in 2021. The data that were submitted for 2021 are based on approximately 7,826,121,178 chickens slaughtered and 50,550,817,859 pounds liveweight produced. Granular flock-level treatment records were available for 75–90% of the birds represented in the 2018–2021 dataset. There was no use of antimicrobials in the hatchery for the years 2020 and 2021. Medically important in-feed antimicrobial use decreased substantially, with all in-feed tetracycline use being eliminated by 2020, and the use of virginiamycin being reduced by more than 97% since 2013. Medically important water-soluble antimicrobials are used for the treatment of disease in broiler production. Use decreased substantially for most water-soluble antimicrobials. The most important diseases necessitating treatment were necrotic enteritis and gangrenous dermatitis as well as E. coli-related disease. A ...
Keywords	broiler chickens ; antimicrobial use ; antimicrobial stewardship ; epidemiological monitoring ; necrotic enteritis ; gangrenous dermatitis ; Veterinary medicine ; SF600-1100
Subject code	333
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: On-farm antimicrobial usage in commercial turkey production in the United States, 2013–2021

Randall S. Singer / Nora F. D. Schrag / Isabel Ricke / Michael D. Apley

Frontiers in Veterinary Science, Vol

2023 Volume 10

Abstract	A key component of antimicrobial stewardship is the ability to collect antimicrobial use data and ultimately use this information to ensure that administrations are necessary and effective. National antimicrobial sales data cannot help in this capacity because the data lack context, for example, details concerning target species and disease indication. The objective of this study was to continue the development of a system for collecting flock-level on-farm antimicrobial use data from the U.S. turkey industry and to have it be representative of national turkey production in the U.S. This study utilized a public-private partnership to enable collection and protection of sensitive flock-level data from an extremely large industry while releasing deidentified and aggregated information regarding the details of antimicrobial use on U.S. turkey farms over time. Participation was voluntary. Data were collected for the period 2013 through 2021 and are reported on a calendar year basis. Using production statistics from USDA:NASS as a denominator, the data supplied by participating companies represented approximately 67.3% of turkey production in the U.S. in 2013, approximately 69.1% in 2017, and approximately 71.4% in 2021. The data that were submitted for 2021 are based on approximately 149,000,192 turkeys slaughtered and 4,929,773,506 pounds liveweight produced. Detailed prescription records representing approximately 60–70% of the birds were available for the 2018–2021 dataset. The estimated percentage of turkey poults placed that received hatchery antimicrobials decreased from 96.9% in 2013 to 40.5% in 2021. The use of in-feed antimicrobials was practically eliminated, with in-feed tetracycline being the only medically important antimicrobial used in 2021. Use of in-feed tetracyclines decreased approximately 80% between 2013 and 2021. Water-soluble antimicrobial use declined over the study period. Between 2013 and 2021, water-soluble penicillin use decreased approximately 41% but water-soluble tetracycline use ...
Keywords	turkeys ; antimicrobial use ; antimicrobial stewardship ; epidemiological monitoring ; bacterial enteritis ; clostridial dermatitis ; Veterinary medicine ; SF600-1100
Subject code	333
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Antimicrobial use in 20 U.S. beef feedyards: 2018-2019.

Apley, Michael D / Schrag, Nora F D / Amrine, David E / Lubbers, Brian V / Singer, Randall S

Frontiers in veterinary science

2023 Volume 10, Page(s) 1056362

Abstract: The objective of this study was to report antimicrobial use in a convenience sample of U.S. beef feedyards for the years 2018 and 2019. In addition to antimicrobial use metrics, also reported are the indications for antimicrobial use and outcomes related ...

Abstract	The objective of this study was to report antimicrobial use in a convenience sample of U.S. beef feedyards for the years 2018 and 2019. In addition to antimicrobial use metrics, also reported are the indications for antimicrobial use and outcomes related to these indications. Antimicrobial use is characterized at the study and feedyard levels for a total of 1,141,846 head of cattle in 20 U.S. feedyards. Antimicrobial use is reported as milligrams of active antimicrobial ingredient per kilogram of liveweight sold (mg/kg-LW) and regimens of antimicrobials per animal year (Reg/AY). Regimens are described by antimicrobial class within use category as characterized by mg of active antimicrobial product per regimen (mg/Reg) and calendar days of administration per regimen (CDoA/Reg). A total of 1,128,515 regimens of medically important antimicrobials were captured from records. The number of regimens/100 head-in (Reg/100 head-in) are described in a subset of 10 feedyards with adequate data granularity to directly determine indications for antimicrobial administration. For the indications of bovine respiratory disease (BRD), Lameness (Lame), Liver Abscess Control (LAC), and Other (e.g., central nervous system disease, cellulitis) the Reg/100 head-in study-level values are 37.1, 0.8, 98.4, and 0.7, respectively, for 2018, with similar values for 2019. The regimens for BRD are further categorized in these 10 feedyards by the use categories in-feed, control of BRD, and individual animal therapy, yielding study level values of 4.6, 19.6, and 12.9 Reg/100 head-in, respectively, for 2018, with similar values for 2019. Outcomes of therapy for individual animal treatment of BRD, Lame, and Other are reported as treatment success, retreatment, or mortality by 30 days after the initial therapy of an animal for a disease. Treatment success rates (no treatment or mortality in the next 30 days) for 2018 in the 10 feedyards with sufficient data granularity are 76.5, 86.5, and 83.0% for BRD, Lame, and Other, respectively. The comparison of these results with other reports of antimicrobial use in North American feedyards highlights how differing approaches in calculating metric values may result in substantially different conclusions regarding antimicrobial use, especially in relation to long-duration uses.
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1056362
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Article: The association of multiple metrics for evaluating antimicrobial use in U.S. beef feedyards.

Apley, Michael D / Schrag, Nora F D / Amrine, David E / Lubbers, Brian V / Singer, Randall S

Frontiers in veterinary science

2023 Volume 9, Page(s) 1056476

Abstract: In order to accurately portray antimicrobial use in food animals, the need for standardized metrics, and an understanding of the characteristics of different metrics, has long been recognized. Fourteen U.S. feedyards were used to evaluate the effects of ... ...

Abstract	In order to accurately portray antimicrobial use in food animals, the need for standardized metrics, and an understanding of the characteristics of different metrics, has long been recognized. Fourteen U.S. feedyards were used to evaluate the effects of using centralized constants such as defined daily dose (DDD) and defined course dose (DCD) applied to the weight of medically important antimicrobials by class (mg) as opposed to using electronic individual animal treatment records and lot level in-feed antimicrobial records obtained from the same population. Three numerators were calculated directly from recorded data for each drug product: the number of antimicrobial regimens associated with indication (Reg), milligrams of drug administered per regimen (mg), and calendar days of administration for each regimen (CDoA). There were four use indications to which numerators were assigned: liver abscess control (LAC), bovine respiratory disease (BRD), lameness (lame), or all other indications combined (other). Three denominators were also calculated directly from the data, these being the number of days animals were present (head days), number of cattle received (head in), and kilograms of live weight sold (kg-LW). Numerators and denominators were calculated at the lot level. The use of DDD or DCD was explored to determine how their use would affect interpretation of comparisons between lots or feedyards. At the lot level across both study years, the lot estimate of nDDD differed from the CDoA value by >25% in 49.2% of the lots. The number of Defined Course Doses (nDCD) was then compared to the number of Regimens (Reg). Comparing nDCD to Reg at the lot level across both study years, the lot estimate of nDCD differed from the Reg value by >25% in 46.4% of lots. Both year and metric were also shown to affect numerical feedyard ranking by antimicrobial use according to seven different metrics. The analysis reported here adds to the body of literature reporting substantial effects of metric choice on the conclusions drawn from comparing antimicrobial use across multiple production sites.
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.1056476
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Article ; Online: Effects of simulation-based flipped classroom in developing head and neck examination skills in dental students.

Fischer, Kathleen M / Sekula, Michael N / Hannigan, Joseph D / Vaught, Randall L / House, Holly / De Souza, Grace M / Williams, Tarin T

Journal of dental education

2024

Abstract: Objectives: To evaluate the effectiveness of a simulation-based flipped classroom in developing dental students' head and neck examination skills.: Methods: Second-year dental students (n = 118) participated in a simulation-based flipped classroom ... ...

Abstract	Objectives: To evaluate the effectiveness of a simulation-based flipped classroom in developing dental students' head and neck examination skills. Methods: Second-year dental students (n = 118) participated in a simulation-based flipped classroom experience. A pre-class recorded lecture and video were posted online one week before the simulation date. In class, students completed a pre-quiz assessing pre-class coursework understanding of head and neck examination content. Then, students attended a question-and-answer session before the patient simulation. A formative assessment of head and neck examination simulation on a patient in the clinic was completed. Lastly, students completed an in-class post-quiz assessing understanding of head and neck examination content after the simulation, classroom simulation discussion, and open-response survey. Results: Student post-quiz scores were significantly higher than pre-quiz scores, with an average improvement of 4.8 ± 7.2 percentage points. There was no difference between male and female improvement in scores. Student survey responses indicated that students liked combining simulation and flipped classroom methodology, flexibility with their schedules, learning at their pace, and opportunities for a deeper level of learning. Students reported wanting more practice sessions for their technical skills and more accessibility to faculty. Conclusions: According to this study's results, students had significantly higher post-quiz scores than pre-quiz scores and reported positive perceptions of this combined teaching technique. A simulation-based flipped classroom might be an effective teaching approach for developing head and neck examination skills that can be applied at other dental facilities with potentially similar results.
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	410579-5
ISSN	1930-7837 ; 0022-0337
ISSN (online)	1930-7837
ISSN	0022-0337
DOI	10.1002/jdd.13490
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Article ; Online: Harnessing the DNA Repair Pathway in Breast Cancer: Germline Mutations/Polymorphisms in Breast Radiation.

Green, Michael D / Brenneman, Randall / Powell, Simon N / Bergom, Carmen

Seminars in radiation oncology

2022 Volume 32, Issue 3, Page(s) 298–302

Abstract: Molecular profiling facilitates opportunities for personalization of breast cancer management. Increasing availability of germline and somatic sequencing provides insight into predictors of treatment efficacy and treatment tolerance of patients with ... ...

Abstract	Molecular profiling facilitates opportunities for personalization of breast cancer management. Increasing availability of germline and somatic sequencing provides insight into predictors of treatment efficacy and treatment tolerance of patients with breast cancer. The presence of pathologic mutations can guide patient selection for breast conserving surgery vs mastectomy. However, our understanding of the interplay between genetic variants and radiotherapy responses and side effects remains incomplete. Here we review the available data on germline mutations and polymorphisms in breast cancer. We also outline their association with treatment tolerance, locoregional outcomes, and ongoing efforts to transform these insights into more effective treatment strategies in combination with radiotherapy.
MeSH term(s)	Breast Neoplasms/genetics ; Breast Neoplasms/radiotherapy ; DNA Repair/genetics ; Female ; Germ-Line Mutation ; Humans ; Mastectomy ; Mastectomy, Segmental
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2022.01.011
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