196 results on '"Thomas MK"'
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2. The role of a single-shot higher-valency pneumococcal vaccine in overcoming challenges regarding invasive pneumococcal disease in Hong Kong
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Christopher KM Hui, Ivan FN Hung, Bing Lam, Ada WC Lin, Thomas MK So, Andrew TY Wong, and Martin CS Wong
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- 2023
3. Metabolic Consequences of TCF7L2 Deficiency in Mice.
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Kaur, V, primary, Wood, J, additional, Hall, JL, additional, and Thomas, MK, additional
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- 2010
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4. Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency
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Völkl, Thomas MK, Simm, Diemud, Körner, Antje, Kiess, Wieland, Kratzsch, Jürgen, and Dörr, Helmuth G
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- 2009
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5. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial
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Janssen, Harry LA, van Zonneveld, Monika, Senturk, Hakan, Zeuzem, Stefan, Akarca, Ulus S, Cakaloglu, Yilmaz, Simon, Christopher, So, Thomas MK, Gerken, Guido, de Man, Robert A, Niesters, Hubert GM, Zondervan, Pieter, Hansen, Bettina, and Schalm, Solko W
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- 2005
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6. Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine
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van Zonneveld, Monika, Zondervan, Pieter E, Cakaloglu, Yilmaz, Simon, Christopher, Akarca, Ulus S, So, Thomas MK, Flink, Hajo J, de Man, Robert A, Schalm, Solko W, and Janssen, Harry LA
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- 2006
7. Health-related quality of life of Southern Chinese with chronic hepatitis B infection
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Lam Elegance TP, Lam Cindy LK, Lai CL, Yuen MF, Fong Daniel YT, and So Thomas MK
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection. Aim To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL. Methods 520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC) were interviewed with a structured questionnaire, the SF-36 Health Survey version 2 (SF-36v2), and the Chronic Liver Disease Questionnaire (CLDQ). The differences in SF-6D health preference values and SF-36v2 scores between each CHB group and Hong Kong population norms were assessed by t-test. ANOVA was used to compare the mean SF-6D health preference, SF-36v2 scores, and CLDQ scores among CHB groups. Multiple linear regressions were performed to identify determinants of HRQOL. Results CHB patients had significantly lower SF-36v2 scores than the population norm. The SF-6D values of CHB patients with uncomplicated disease, impaired liver function, HCC and cirrhosis were 0.755, 0.745, 0.720 and 0.701, respectively, all significantly lower than the population norm of 0.787. Advanced stage of CHB illness, anti-viral treatment, bilirubin level, psychological co-morbidity, younger age and female were associated with poorer HRQOL. Conclusion CHB infection had a negative impact on HRQOL. There was a progressive decrease in health preference values with CHB disease progression. The results can be used for the estimation of quality adjusted life years (QALYs) for CHB patients in cost effectiveness or cost utility studies. Trial Registration http://www.hkclinicaltrials.com; HKCTR-151.
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- 2009
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8. Methodological Framework for World Health Organization Estimates of the Global Burden of Foodborne Disease
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Devleesschauwer, B, Haagsma, Juanita, Angulo, FJ, Bellinger, DC, Cole, D, Dopfer, D, Fazil, A, Fevre, EM, Gibb, HJ, Hald, T, Kirk, MD, Lake, RJ, de Noordhout, CM, Mathers, CD, McDonald, SA, Pires, SM, Speybroeck, N, Thomas, MK, Torgerson, PR, Wu, F, Havelaar, AH, Praet, N, Devleesschauwer, B, Haagsma, Juanita, Angulo, FJ, Bellinger, DC, Cole, D, Dopfer, D, Fazil, A, Fevre, EM, Gibb, HJ, Hald, T, Kirk, MD, Lake, RJ, de Noordhout, CM, Mathers, CD, McDonald, SA, Pires, SM, Speybroeck, N, Thomas, MK, Torgerson, PR, Wu, F, Havelaar, AH, and Praet, N
- Abstract
Background The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization to estimate the global burden of foodborne diseases (FBDs). This paper describes the methodological framework developed by FERG's Computational Task Force to transform epidemiological information into FBD burden estimates. Methods and Findings The global and regional burden of 31 FBDs was quantified, along with limited estimates for 5 other FBDs, using Disability-Adjusted Life Years in a hazard-and incidence-based approach. To accomplish this task, the following workflow was defined: outline of disease models and collection of epidemiological data; design and completion of a database template; development of an imputation model; identification of disability weights; probabilistic burden assessment; and estimating the proportion of the disease burden by each hazard that is attributable to exposure by food (i.e., source attribution). All computations were performed in R and the different functions were compiled in the R package 'FERG'. Traceability and transparency were ensured by sharing results and methods in an interactive way with all FERG members throughout the process. Conclusions We developed a comprehensive framework for estimating the global burden of FBDs, in which methodological simplicity and transparency were key elements. All the tools developed have been made available and can be translated into a user-friendly national toolkit for studying and monitoring food safety at the local level.
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- 2015
9. Health-related quality of life of Southern Chinese with chronic hepatitis B infection
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Cindy L. K. Lam, CL Lai, Elegance Tp P. Lam, Thomas Mk K. So, Daniel Yt T. Fong, and MF Yuen
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Adult ,Questionnaires ,Male ,China ,medicine.medical_specialty ,Cirrhosis ,Psychometrics ,Cost effectiveness ,Population ,Disease ,China - ethnology ,Chronic liver disease ,lcsh:Computer applications to medicine. Medical informatics ,Hepatitis B, Chronic ,Surveys and Questionnaires ,Internal medicine ,medicine ,Health Status Indicators ,Humans ,education ,Aged ,education.field_of_study ,Analysis of Variance ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,General Medicine ,Hepatitis B ,Middle Aged ,medicine.disease ,Health Surveys ,Quality-adjusted life year ,Hepatitis B, Chronic - psychology ,Hepatocellular carcinoma ,Physical therapy ,Quality of Life ,lcsh:R858-859.7 ,Hong Kong ,Female ,business - Abstract
Background: Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection. Aim: To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL. Methods: 520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC) were interviewed with a structured questionnaire, the SF-36 Health Survey version 2 (SF-36v2), and the Chronic Liver Disease Questionnaire (CLDQ). The differences in SF-6D health preference values and SF-36v2 scores between each CHB group and Hong Kong population norms were assessed by t-test. ANOVA was used to compare the mean SF-6D health preference, SF-36v2 scores, and CLDQ scores among CHB groups. Multiple linear regressions were performed to identify determinants of HRQOL. Results: CHB patients had significantly lower SF-36v2 scores than the population norm. The SF-6D values of CHB patients with uncomplicated disease, impaired liver function, HCC and cirrhosis were 0.755, 0.745, 0.720 and 0.701, respectively, all significantly lower than the population norm of 0.787. Advanced stage of CHB illness, anti-viral treatment, bilirubin level, psychological co-morbidity, younger age and female were associated with poorer HRQOL. Conclusion: CHB infection had a negative impact on HRQOL. There was a progressive decrease in health preference values with CHB disease progression. The results can be used for the estimation of quality adjusted life years (QALYs) for CHB patients in cost effectiveness or cost utility studies. © 2009 Lam et al; licensee BioMed Central Ltd., link_to_subscribed_fulltext
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- 2009
10. Estimation du fardeau des maladies d'origine alimentaire au Canada
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Thomas, MK, primary and Murray, R, additional
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- 2014
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11. Phytoplankton niches, traits and eco-evolutionary responses to global environmental change
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Litchman, E, primary, Edwards, KF, additional, Klausmeier, CA, additional, and Thomas, MK, additional
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- 2012
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12. Facial sculpting: Comprehensive approach for aesthetic correction of round face
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Thomas, MK, primary, D′Silva, JA, additional, and Borole, AJ, additional
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- 2012
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13. New Strain Acquisition ofKlebsiellaSpp,EnterobacterSpp andEscherichia coliin COPD Is Not Associated with Exacerbations.
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Jung, J, primary, Thomas, MK, additional, Sethi, R, additional, Tekwe, CD, additional, Murphy, TF, additional, and Sethi, S, additional
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- 2009
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14. Estimating the burden of food-borne illness in Canada.
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Thomas, MK and Murray, R.
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FOODBORNE diseases ,CANADA. Public Health Agency ,CLOSTRIDIUM perfringens ,FOOD industry ,PATHOGENIC microorganisms - Abstract
The Public Health Agency of Canada estimates that each year about 1 in 8 Canadians (4 million people) get sick from the food they eat. Four pathogens cause about 90% of the 1.6 million illnesses caused by known pathogens: Norovirus (1 million cases), Clostridium perfringens (177,000 cases), Campylobacter (145,000 cases) and nontyphoidal Salmonella (88,000 cases). These estimates are based on multiple complementary disease surveillance systems and the peer-reviewed literature. Understanding the burden of food-borne illness is useful for decision-makers, supporting the development of food safety and public health interventions, for research and for consumer education. Future efforts will focus on estimating the number of food-borne hospitalizations and deaths, the economic cost of food-borne illness and the burden of water-borne illness in order to provide crucial information to support research, policy and action. [ABSTRACT FROM AUTHOR]
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- 2014
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15. Burden of acute gastrointestinal illness in Gálvez, Argentina, 2007.
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Thomas MK, Perez E, Majowicz SE, Reid-Smith R, Albil S, Monteverde M, McEwen SA, Thomas, M Kate, Perez, Enrique, Majowicz, Shannon E, Reid-Smith, Richard, Albil, Silvia, Monteverde, Marcos, and McEwen, Scott A
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This study evaluated the magnitude and distribution of acute gastrointestinal illness (GI) in Gálvez, Argentina, and assessed the outcome of a seven-day versus 30-day recall period in survey methodology. A cross-sectional population survey, with either a seven-day or a 30-day retrospective recall period, was conducted through door-to-door visits to randomly-selected residents during the 'high' and the 'low' seasons of GI in the community. Comparisons were made between the annual incidence rates obtained using the seven-day and the 30-day recall period. Using the 30-day recall period, the mean annual incidence rates was 0.43 (low season of GI) and 0.49 (high season of GI) episodes per person-year. Using the seven-day recall period, the mean annual incidence rate was 0.76 (low season of GI) and 2.66 (high season of GI) episodes per person-year. This study highlights the significant burden of GI in a South American community and confirms the importance of seasonality when investigating GI in the population. The findings suggest that a longer recall period may underestimate the burden of GI in retrospective population surveys of GI. [ABSTRACT FROM AUTHOR]
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- 2010
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16. Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt.
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Yano T, Liu Z, Donovan J, Thomas MK, Habener JF, Yano, Tatsuya, Liu, Zhengyu, Donovan, Jennifer, Thomas, Melissa K, and Habener, Joel F
- Abstract
Objective: Diabetes is caused by a deficiency of pancreatic beta-cells that produce insulin. Approaches to enhance beta-cell mass by increasing proliferation and survival are desirable. We determined whether stromal cell-derived factor (SDF)-1/CXCL12 and its receptor, CX chemokine receptor (CXCR)4, are important for the survival of beta-cells.Research Design and Methods: Mouse pancreata and clonal beta-cells were examined for expression of SDF-1 and CXCR4, activation of AKT and downstream signaling pathways by SDF-1, and protection against apoptosis and diabetes induced by streptozotocin (STZ).Results: CXCR4 is expressed in beta-cells, and SDF-1 is expressed in microvascular endothelial cells within the islets and in surrounding interstitial stromal tissue. Transgenic mice overexpressing SDF-1 within their beta-cells (RIP-SDF-1 mice) are resistant to STZ-induced beta-cell apoptosis and diabetes. In MIN6 beta-cells, a CXCR4 antagonist (AMD3100) induces apoptosis, increases reactive oxygen species, decreases expression levels of the anti-apoptotic protein Bcl-2, and reduces phosphorylation of the proapoptotic protein Bad. Active phosphorylated prosurvival kinase Akt is increased both in the beta-cells of RIP-SDF-1 mice and in INS-1 cells treated with SDF-1 and sensitive to AMD3100. Inhibition of AKT expression by small interfering RNA attenuates the ameliorative effects of SDF-1 on caspase-dependent apoptosis induced by thapsigargin or glucose deprivation in INS-1 beta-cells. Specific inhibition of Akt activation by a soluble inhibitor (SH-5) reverses the anti-apoptotic effects of SDF-1 in INS-1 cells and mouse islets.Conclusions: SDF-1 promotes pancreatic beta-cell survival via activation of Akt, suggesting that SDF-1 agonists may prove beneficial for treatment of diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2007
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17. A role of high impact weather events in waterborne disease outbreaks in Canada, 1975 - 2001.
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Thomas MK, Charron DF, Waltner-Toews D, Schuster C, Maarouf AR, and Holt JD
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Recent outbreaks of Escherichia coli O157:H7, Campylobacter, and Cryptosporidium have heightened awareness of risks associated with contaminated water supply. The objectives of this research were to describe the incidence and distribution of waterborne disease outbreaks in Canada in relation to preceding weather conditions and to test the association between high impact weather events and waterborne disease outbreaks. We examined extreme rainfall and spring snowmelt in association with 92 Canadian waterborne disease outbreaks between 1975 and 2001, using case-crossover methodology. Explanatory variables including accumulated rainfall, air temperature, and peak stream flow were used to determine the relationship between high impact weather events and the occurrence of waterborne disease outbreaks. Total maximum degree-days above 0 degrees C and accumulated rainfall percentile were associated with outbreak risk. For each degree-day above 0 degrees C the relative odds of an outbreak increased by a factor of 1.007 (95% confidence interval [CI] = 1.002 - 1.012). Accumulated rainfall percentile was dichotomized at the 93rd percentile. For rainfall events greater than the 93rd percentile the relative odds of an outbreak increased by a factor of 2.283 (95% [CI] = 1.216 - 4.285). These results suggest that warmer temperatures and extreme rainfall are contributing factors to waterborne disease outbreaks in Canada. This could have implications for water management and public health initiatives. [ABSTRACT FROM AUTHOR]
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- 2006
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18. Fluid ingestion attenuates the decline in VO2peak associated with cardiovascular drift.
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Ganio MS, Wingo JE, Carroll CE, Thomas MK, and Cureton K
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- 2006
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19. Hypovitaminosis D in medical inpatients.
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Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS, Thomas, M K, Lloyd-Jones, D M, Thadhani, R I, Shaw, A C, Deraska, D J, Kitch, B T, Vamvakas, E C, Dick, I M, Prince, R L, and Finkelstein, J S
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Background: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown.Methods: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward.Results: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent.Conclusions: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency. [ABSTRACT FROM AUTHOR]- Published
- 1998
20. The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes
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Jennifer N. Todd, Andrew W. Taylor, Geoffrey A. Walford, Maegan Harden, Deborah J. Wexler, Jaclyn Davis, Melissa K. Thomas, Janet Lo, Varinderpal Kaur, Jose C. Florez, Ling Chen, Katherine R. Littleton, Rachel J. Ackerman, Rebecca R. Fanelli, Bindu Chamarthi, Paul L. Huang, Corinne Barbato, Liana K. Billings, Allison B. Goldfine, A. Sofia Warner, Elliot S. Stolerman, Alisa K. Manning, Allan F. Moore, Sabina Q. Khan, Richard W. Grant, Rita M. McCarthy, Margo S. Hudson, Chunmei Huang, Marlene Fernandez, Alicia M. Hernandez, Rosa Bui, Laurel Garber, Amelia Lanier, Natalia Colomo, [Walford,GA, Colomo,N, Todd,JN, Billings,LK, Fernandez,M, Warner,AS, Davis,J, Littleton,KR, Hernandez,AM, Fanelli,RR, Lanier,A, Ackerman,RJ, Khan,SQ, Stolerman,ES, Moore,AF, Kaur,V, Taylor,A, Chen,L, Manning,AK, Florez,JC] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America. [Walford,GA, Wexler,D, Thomas,MK, Florez,JC] Diabetes Research Center, Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America. [Walford,GA, Huang,C, Huang,P, Lo,J, Goldfine,A, Florez,JC] Harvard Medical School, Boston, Massachusetts, United States of America. [Colomo,N] Department of Endocrinology and Nutrition. Hospital Universitario Regional de Málaga. Instituto de Investigación Biomédica de Málaga (IBIMA). Málaga, Spain. [Todd,JN] Boston Children’s Hospital, Boston, Massachusetts, United States of America. [Billings,LK, ] Division of Endocrinology and Metabolism, NorthShore University Health System, Evanston, Illinois, United States of America. [Chamarthi,B] Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America. [Chamarthi,B, McCarthy,RM, Hudson,MS] Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America. [Barbato,C, Bui,R, Garber,L, Goldine,A] Joslin Diabetes Center, Boston, Massachusetts, United States of America. [Harden,M] Genomics Platform, Broad Institute, Cambridge, Massachusetts, United States of America. [Grant,RW] Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America., This work was conducted with support from National Institutes of Health/NIDDK awards R01 DK088214, R03 DK077675, and P30 DK036836, from the Joslin Clinical Research Center from its philanthropic donors, and and the Harvard Catalyst: The Harvard Clinical and translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Awards M01-RR-01066, 1 UL1 RR025758-04 and 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers).
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Blood Glucose ,Male ,Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,medicine.medical_treatment ,lcsh:Medicine ,Type 2 diabetes ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Hipoglicemiantes ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Insulina ,Insulin ,lcsh:Science ,Genetics ,Glucose tolerance test ,Prueba de tolerancia a la glucosa ,Multidisciplinary ,medicine.diagnostic_test ,Predisposición genética a la enfermedad ,Middle Aged ,Polimorfismo de nucleótido único ,Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] ,Metformin ,3. Good health ,Phenotype ,Treatment Outcome ,Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::Metformin [Medical Subject Headings] ,Female ,Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacogenetics [Medical Subject Headings] ,Alelos ,Fenotipo ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Clinical Chemistry Tests::Blood Chemical Analysis::Glucose Tolerance Test [Medical Subject Headings] ,Transcription Factor 7-Like 2 Protein ,medicine.drug ,Research Article ,Adult ,Blood sugar ,Check Tags::Male [Medical Subject Headings] ,Hypoglycemia ,Polymorphism, Single Nucleotide ,Diabetes mellitus ,medicine ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Proteína 2 similar al factor de transcripción 7 ,Humans ,Hypoglycemic Agents ,Genetic Predisposition to Disease ,Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] ,Alleles ,Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::Insulins [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Aged ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,business.industry ,lcsh:R ,Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings] ,glipicida ,Glucose Tolerance Test ,medicine.disease ,Biomarcadores ,Check Tags::Female [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::TCF Transcription Factors::Transcription Factor 7-Like 2 Protein [Medical Subject Headings] ,Diabetes Mellitus, Type 2 ,Pharmacogenetics ,Diabetes Mellitus, Tipo II ,Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Sulfones::Sulfonylurea Compounds::Glipizide [Medical Subject Headings] ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic Agents [Medical Subject Headings] ,lcsh:Q ,Resultado del tratamiento ,business ,Biomarkers ,Glipizide ,Glucosa sanguínea ,Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood Glucose [Medical Subject Headings] - Abstract
ClinicalTrials.gov NCT01762046; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; OBJECTIVE Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. METHODS All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. RESULTS Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. CONCLUSIONS SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01762046. Yes
- Published
- 2015
21. Comparison of 6 handheld ultrasound devices by point-of-care ultrasound experts: a cross-sectional study.
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Perez-Sanchez A, Johnson G, Pucks N, Soni RN, Lund TJS, Andrade AJ, Le MT, Solis-McCarthy J, Wong T, Ashraf A, Kumar AD, Banauch GI, Verner JR, Sodhi A, Thomas MK, LoPresti C, Schmitz H, Koratala A, Hunninghake J, Manninen E, Candotti C, Minami T, Mathews BK, Bandak G, Sauthoff H, Mayo-Malasky H, Cho J, Villalobos N, Proud KC, Boesch B, Fenton Portillo F, Reierson K, Malik M, Abbas F, Johnson T, Haro EK, Mader MJ, Mayo P, Franco-Sadud R, and Soni NJ
- Abstract
Background: Point-of-care ultrasound (POCUS) has emerged as an essential bedside tool for clinicians, but lack of access to ultrasound equipment has been a top barrier to POCUS use. Recently, several handheld ultrasound devices ("handhelds") have become available, and clinicians are seeking data to guide purchasing decisions. Few comparative studies of different handhelds have been done. We conducted a cross-sectional study comparing 6 handhelds readily available in the United States (Butterfly iQ +
™ by Butterfly Network Inc.; Clarius™ by Clarius Mobile Health; Kosmos™ by EchoNous; TE Air™ by Mindray; Vscan Air™ SL and CL by General Electric; and Lumify™ by Philips Healthcare). A multi-specialty group of physician POCUS experts (n = 35) acquired three standard ultrasound views (abdominal right upper quadrant, cardiac apical 4-chamber, and superficial neck and lung views) in random order on the same standardized patients and rated the image quality. Afterward, a final survey of the overall ease of use, image quality, and satisfaction of each handheld was completed., Results: Thirty-five POCUS experts specializing in internal medicine/hospital medicine, critical care, emergency medicine, and nephrology acquired and rated right upper quadrant, apical 4-chamber, and superficial neck and lung views with 6 different handhelds. For image quality, the highest-rated handhelds were Vscan Air™ for the right upper quadrant view, Mindray TE Air™ for the cardiac apical 4-chamber view, and Lumify™ for superficial views of the neck and lung. Overall satisfaction with image quality was highest with Vscan Air™ , Lumify™ , and Mindray, while overall satisfaction with ease of use was highest with Vscan Air™ . The 5 most desirable characteristics of handhelds were image quality, ease of use, portability, probe size, and battery life. Ultimately, all 6 handhelds had notable advantages and disadvantages, with no single device having all desired qualities or features., Conclusions: The overall satisfaction with image quality was rated highest with Vscan Air™ , Lumify™ , and Mindray TE Air™ when acquiring right upper quadrant, apical 4-chamber, and superficial neck and lung views. No single handheld was perceived to be superior in image quality for all views. Vscan Air™ was rated highest for overall ease of use and was the most preferred handheld for purchase by POCUS experts., (© 2024. The Author(s).)- Published
- 2024
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22. Tyrp1 is the mendelian determinant of the Axolotl (Ambystoma mexicanum) copper mutant.
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Cecil RF, Strohl L, Thomas MK, Schwartz JL, Timoshevskaya N, Smith JJ, and Voss SR
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- Animals, Phenotype, Oxidoreductases genetics, Oxidoreductases metabolism, Melanins metabolism, Melanins genetics, Ambystoma mexicanum genetics, Copper metabolism, Polymorphism, Single Nucleotide, Mutation, Pigmentation genetics
- Abstract
Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that when mutated, is associated with lighter than black melanin coloration in animal models and oculocutaneous albinism in humans. Inspection of RNA-Seq reads identified a single nucleotide deletion that is predicted to change the coding frame, introduce a premature stop codon in exon 6 and yield a truncated Tyrp1 protein in copper individuals. Using CRISPR-Cas9 editing, we show that wildtype Tyrp1 crispants exhibit copper pigmentation, thus confirming Tyrp1 as the copper locus. Our results suggest that commercial and hobbyist axolotl populations may harbor useful mutants for biological research., (© 2024. The Author(s).)
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- 2024
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23. Virtual Reality in Cancer Care: Enhancing Knowledge and Reducing Anxiety about Chemotherapy among Patients and Caregivers.
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Thomas MK, Jarrahi AA, Dennie L, Scott S, Lau T, and Johnson A
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- Humans, Female, Male, Middle Aged, Adult, Health Knowledge, Attitudes, Practice, Aged, Antineoplastic Agents therapeutic use, Young Adult, Surveys and Questionnaires, Virtual Reality, Neoplasms psychology, Neoplasms drug therapy, Anxiety, Caregivers psychology
- Abstract
Virtual reality (VR) technology has evolved from entertainment to significant applications in healthcare and education. Despite its potential, there is limited research on the role of VR in cancer care. This study investigates VR's ability to simulate the chemotherapy process, aiming to enhance patients' knowledge and mitigate anxiety associated with chemotherapy. Utilizing a two-arm, mixed-methods pre/post-survey design, the study measured changes in patients' anxiety and knowledge before and after exposure to a VR simulation. Participants ( n = 267) engaged with VR simulations or interactive 360-degree videos depicting the chemotherapy process. Data analyses revealed a significant median increase in chemotherapy knowledge post-exposure to the VR content (z = 12.511, p < 0.001). Demographic factSors significantly influenced perceptions of VR realism and usefulness ( p < 0.05). Additionally, VR exposure was correlated with reduced anxiety levels and improved treatment expectations ( p < 0.05). Participants with higher post-understanding chemotherapy scores considered VR a useful tool for managing anxiety about chemotherapy and recommended VR for other medical procedures ( p < 0.001). These findings underscore VR technology's potential as a valuable tool in cancer treatment, suggesting it can enhance patient education and reduce anxiety, thereby improving patient outcomes during cancer therapy.
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- 2024
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24. Reducing Falls in Hospitalized Children and Adolescents with Cancer and Blood Disorders: A Quality Improvement Journey.
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Morrissey LK, Ho P, Ilowite M, Johnson DA, Nixon CM, Thomas MK, Waitt JA, Wierzchowski A, and Renaud AM
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Background: Falls in hospitalized pediatric patients represent a serious patient safety concern. Children and adolescents with cancer and blood disorders have inherent risk factors that increase the likelihood of injury from falls. The Hematology/Oncology (HO) and Stem Cell Transplant (SCT) inpatient units at Boston Children's Hospital embarked on a multiyear quality improvement journey to reduce inpatient falls in this population., Methods: A targeted Falls Reduction Task Force implemented key initiatives between 2020 and 2023. These include enhancing communication strategies to heighten awareness of the highest fall-risk patients, conducting a formal apparent cause analysis on every fall with injury, and initiating a physical therapy-led program to reduce deconditioning. Outcome measures were total falls, rate of preventable falls with injury per 1000 patient days, and days between preventable falls with injury. Our quality improvement team used statistical process control charts to track changes over time., Results: The combined rate of preventable falls with injury per 1000 patient days decreased from 0.63 in fiscal year (FY) 2020 to 0.25 in 2023. The SCT and HO units achieved a maximum of 442 days and 410 days, respectively, between preventable falls with injury in 2021-2023, compared with 124 and 117 days in 2020. The two units observed a 51% reduction in total falls over 4 years., Conclusions: A multifaceted fall reduction quality initiative effectively reduced preventable falls with injury on pediatric HO and SCT inpatient units, thereby reducing avoidable harm in a vulnerable patient population., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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25. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor.
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Regmi A, Aihara E, Christe ME, Varga G, Beyer TP, Ruan X, Beebe E, O'Farrell LS, Bellinger MA, Austin AK, Lin Y, Hu H, Konkol DL, Wojnicki S, Holland AK, Friedrich JL, Brown RA, Estelle AS, Badger HS, Gaidosh GS, Kooijman S, Rensen PCN, Coskun T, Thomas MK, and Roell W
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- 2024
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26. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.
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Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, and Hartman ML
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- Humans, Male, Female, Middle Aged, Adult, Double-Blind Method, Receptors, Glucagon agonists, Glucagon-Like Peptide-1 Receptor agonists, Liver drug effects, Liver metabolism, Obesity drug therapy, Obesity complications, Aged, Fatty Acids, Peptides, Fatty Liver drug therapy
- Abstract
Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 ., (© 2024. The Author(s).)
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- 2024
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27. Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2).
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Frias JP, De Block C, Brown K, Wang H, Thomas MK, Zeytinoglu M, and Maldonado JM
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- Humans, Male, Female, Middle Aged, Glycated Hemoglobin analysis, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Blood Glucose drug effects, Blood Glucose metabolism, Aged, Adult, Double-Blind Method, Insulin blood, Insulin metabolism, Islets of Langerhans drug effects, Islets of Langerhans metabolism, Treatment Outcome, Glucagon-Like Peptide-2 Receptor, Gastric Inhibitory Polypeptide, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 metabolism, Insulin Resistance, Glucagon-Like Peptides administration & dosage, Glucagon-Like Peptides pharmacology, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Biomarkers blood
- Abstract
Context: In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators., Objective: Explore changes in biomarkers of β-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide., Design: Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks)., Setting: Post hoc analysis of 128 sites in 8 countries., Participants: A total of 1879 participants with type 2 diabetes., Interventions: Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg., Main Outcomes Measures: Change in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin., Results: At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile., Conclusion: In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline β-cell function and insulin resistance, compared with semaglutide., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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28. Conservation applications of niche modeling: Native and naturalized ferns may compete for limited Hawaiian dryland habitat.
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Edwards-Calma K, Jiménez L, Zenil-Ferguson R, Heyduk K, Thomas MK, and Tribble CM
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Premise: Competition from naturalized species and habitat loss are common threats to native biodiversity and may act synergistically to increase competition for decreasing habitat availability. We use Hawaiian dryland ferns as a model for the interactions between land-use change and competition from naturalized species in determining habitat availability., Methods: We used fine-resolution climatic variables and carefully curated occurrence data from herbaria and community science repositories to estimate the distributions of Hawaiian dryland ferns. We quantified the degree to which naturalized ferns tend to occupy areas suitable for native species and mapped the remaining available habitat given land-use change., Results: Of all native species, Doryopteris angelica had the lowest percentage of occurrences of naturalized species in its suitable area while D. decora had the highest. However, all Doryopteris spp. had a higher percentage overlap, while Pellaea ternifolia had a lower percentage overlap, than expected by chance. Doryopteris decora and D. decipiens had the lowest proportions ( < 20%) of suitable area covering native habitat., Discussion: Areas characterized by shared environmental preferences of native and naturalized ferns may decrease due to human development and fallowed agricultural lands. Our study demonstrates the value of place-based application of a recently developed correlative ecological niche modeling approach for conservation risk assessment in a rapidly changing and urbanized island ecosystem., (© 2024 The Author(s). Applications in Plant Sciences published by Wiley Periodicals LLC on behalf of Botanical Society of America.)
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- 2024
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29. Effects of Tirzepatide vs Semaglutide on β-cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test.
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Mather KJ, Mari A, Heise T, DeVries JH, Hua M, Urva S, Coskun T, Haupt A, Heine RJ, Pratt E, Thomas MK, and Milicevic Z
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Context: In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood., Objective: To evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data., Design: A 28-week double-blind, randomized, placebo-controlled trial., Setting: Two clinical research centers in Germany., Patients: Patients with type 2 diabetes treated with metformin., Interventions: Tirzepatide 15 mg, semaglutide 1 mg, placebo., Main Outcome Measures: Glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2-mmol/L glucose (ISR7.2), β-cell glucose (β-CG) sensitivity, insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio., Results: Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < 0.01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < 0.01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < 0.01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < 0.05), showing improved β-CG responsiveness. MMTT-derived β-CG sensitivity was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < 0.01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment., Conclusions: These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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30. Breast Cancer Knowledge Among Amish and Mennonite Women.
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Thomas MK, Gilligan A, Lawson J, and Lau T
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Breast cancer is the most common cancer diagnosis for women in the USA and ranks second in cancer-related deaths. Disproportionately higher breast cancer rates can be found in rural and Appalachian regions due to several social drivers of health, including poverty, access to healthcare, and lack of culturally sensitive health education. Amish and Mennonite communities, religious groups with distinct cultural practices and beliefs, experience lower mammography screening and higher breast cancer mortality rates (among Amish women). This study focuses on knowledge about breast cancer and causes of cancer among Amish and Mennonite women. A total of 473 women participated in the study at 26 separate women's health clinics throughout Ohio, consisting of 348 Amish and 121 Mennonite women, the largest study conducted on breast cancer knowledge spanning dozens of communities. Statistically significant differences were found in total knowledge scores between Amish and Mennonite women (r
pb = .178, n = 466, p = .007), with Amish women having lower scores and stronger beliefs in myths associated with breast cancer cause and symptoms (χ(1) = 7.558, p = .006). Both groups often provided scientifically accurate descriptions of cancer etiology. The majority of participants underestimated breast cancer risk, highlighting the need for culturally appropriate health education programs that consider numeracy and health literacy. By implementing targeted interventions and fostering partnerships with community stakeholders using a multifaceted approach that incorporates cultural sensitivity, community engagement, and collaboration, significant progress can be made towards reducing breast cancer disparities and improving health outcomes., (© 2024. The Author(s).)- Published
- 2024
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31. Associations of plasma sphingolipids with measures of insulin sensitivity, β-cell function, and incident diabetes in Japanese Americans.
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Bae JC, Wander PL, Lemaitre RN, Fretts AM, Sitlani CM, Bui HH, Thomas MK, Leonetti D, Fujimoto WY, Boyko EJ, and Utzschneider KM
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- Female, Humans, Male, Middle Aged, Asian, Ceramides, Cross-Sectional Studies, Sphingolipids, Diabetes Mellitus diagnosis, Diabetes Mellitus epidemiology, Insulin Resistance
- Abstract
Background and Aims: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, β-cell function, and incident diabetes in the Japanese American Community Diabetes Study., Methods and Results: Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), β-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %)., Conclusion: Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)
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- 2024
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32. Effect of Delirium on Interhospital Transfer Outcomes.
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Thomas MK, Kalivas B, Zhang J, Marsden J, Mauldin PD, Moran WP, Hunt K, and Heincelman M
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- Adult, Humans, Retrospective Studies, Hospitalization, Length of Stay, Hospital Mortality, Emergency Service, Hospital, Patient Transfer, Delirium epidemiology
- Abstract
Objectives: Interhospital transfer (IHT) and in-hospital delirium are both independently associated with increased length of stay (LOS), mortality, and discharge to facility. Our objective was to investigate the joint effects between IHT and the presence of in-hospital delirium on the outcomes of LOS, discharge to a facility, and in-hospital mortality., Methods: This was a single-center retrospective cohort study of 25,886 adult hospital admissions at a tertiary-care academic medical center. Staged multivariable logistic and linear regression models were used to evaluate the association between IHT status and the outcomes of discharge to a facility, LOS, and mortality while considering the joint impact of delirium. The joint effects of IHT status and delirium were evaluated by categorizing patients into one of four categories: emergency department (ED) admissions without delirium, ED admissions with delirium, IHT admissions without delirium, and IHT admissions with delirium. The primary outcomes were LOS, in-hospital mortality, and discharge disposition., Results: The odds of discharge to a facility were 4.48 times higher in admissions through IHT with delirium when compared with ED admissions without delirium. IHT admissions with delirium had a 1.97-fold (95% confidence interval 1.88-2.06) longer LOS when compared with admission through the ED without delirium. Finally, admissions through IHT with delirium had 3.60 (95% confidence interval 2.36-5.49) times the odds of mortality when compared with admissions through the ED without delirium., Conclusions: The relationship between IHT and delirium is complex, and patients with IHT combined with in-hospital delirium are at high risk of longer LOS, discharge to a facility, and mortality.
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- 2024
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33. Improvements in post-challenge lipid response following tirzepatide treatment in patients with type 2 diabetes.
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Mather KJ, Coskun T, Pratt EJ, Milicevic Z, Weerakkody G, Thomas MK, Haupt A, and Ruotolo G
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- Humans, Gastric Inhibitory Polypeptide, Lipids, Glucagon-Like Peptide-1 Receptor, Hypoglycemic Agents therapeutic use, Diabetes Mellitus, Type 2 drug therapy
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- 2024
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34. Designing More Informative Multiple-Driver Experiments.
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Thomas MK and Ranjan R
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- Nutrients, Oxygen, Temperature, Ecosystem, Ecology
- Abstract
For decades, multiple-driver/stressor research has examined interactions among drivers that will undergo large changes in the future: temperature, pH, nutrients, oxygen, pathogens, and more. However, the most commonly used experimental designs-present-versus-future and ANOVA-fail to contribute to general understanding or predictive power. Linking experimental design to process-based mathematical models would help us predict how ecosystems will behave in novel environmental conditions. We review a range of experimental designs and assess the best experimental path toward a predictive ecology. Full factorial response surface, fractional factorial, quadratic response surface, custom, space-filling, and especially optimal and sequential/adaptive designs can help us achieve more valuable scientific goals. Experiments using these designs are challenging to perform with long-lived organisms or at the community and ecosystem levels. But they remain our most promising path toward linking experiments and theory in multiple-driver research and making accurate, useful predictions.
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- 2024
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35. Estimating the burden of illness caused by domestic waterborne Legionnaires' disease in Canada: 2015-2019.
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McMullen CKM, Dougherty B, Medeiros DT, Yasvinski G, Sharma D, and Thomas MK
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- Humans, Canada epidemiology, Cost of Illness, Legionnaires' Disease epidemiology, Legionnaires' Disease microbiology, Legionella pneumophila, Legionellosis epidemiology, Legionellosis microbiology, Legionella
- Abstract
Legionellosis is a disease caused by the bacterium Legionella that most commonly presents as Legionnaires' disease (LD), a severe form of pneumonia. From 2015 to 2019, an average of 438 LD cases per year were reported in Canada. However, it is believed that the actual number of cases is much higher, since LD may be underdiagnosed and underreported. The purpose of this study was to develop an estimate of the true incidence of illnesses, hospitalizations, and deaths associated with LD in Canada. Values were derived using a stochastic model, based on Canadian surveillance data from 2015 to 2019, which were scaled up to account for underdiagnosis and underreporting. Overall, there were an estimated 1,113 (90% CrI: 737-1,730) illnesses, 1,008 (90% CrI: 271-2,244) hospitalizations, and 34 (90% CrI: 4-86) deaths due to domestically acquired waterborne LD annually in Canada from 2015 to 2019. It was further estimated that only 36% of illnesses and 39% of hospitalizations and deaths were captured in surveillance, and that 22% of illnesses were caused by Legionella serogroups and species other than Legionella pneumophila serogroup 1 (non-Lp1). This study highlights the true burden and areas for improvement in Canada's surveillance and detection of LD.
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- 2024
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36. Point-counterpoint: Should point-of-care ultrasound be a required skill of hospitalists?
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Thomas MK, Conner SM, Maw A, and Soni NJ
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- Humans, Point-of-Care Systems, Ultrasonography, Hospitalists
- Published
- 2023
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37. Development and Assessment of Simulation-Based Point-of-Care Ultrasound Curriculum in Undergraduate Medical Education.
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Hagood NL, Klaybor M, Srivastava R, McManigle W, Huggins JT, Shah PV, Heincelman ME, and Thomas MK
- Abstract
Objectives: Implementation barriers and lack of standardized point-of-care ultrasound (POCUS) curricula make the development of effective POCUS curricula and methods of assessment challenging. The authors aim to develop a longitudinal POCUS curriculum through staged intervention. In the first stage, the authors hypothesized that the use of high-fidelity ultrasound simulation during the Internal Medicine clerkship would improve POCUS confidence and knowledge among medical students, minimizing the need for trained faculty., Methods: A quasi-experimental study of third-year students on the Internal Medicine clerkship at a large academic medical center in the United States was performed assessing the efficacy of ultrasound simulation use. The control group consisted of students who received baseline POCUS education during teaching rounds but did not have access to the ultrasound simulator. The experimental group consisted of students who, in addition to baseline POCUS education, had access to a high-fidelity ultrasound simulator throughout the clerkship for a minimum of 1 hour per week. Students in both the control and experimental groups completed a pre- and post-intervention confidence survey and knowledge-based examination., Results: Eighty-two percent (50/61) of students completed pre- and post-tests, with the control group demonstrating no significant difference in POCUS confidence or knowledge. After exposure to the ultrasound simulator, the experimental group demonstrated statistically significant improvement in POCUS confidence and overall POCUS knowledge ( p < .01)., Conclusion: The use of high-fidelity ultrasound simulation can improve POCUS confidence and knowledge among medical students while addressing common barriers to the implementation of a POCUS curriculum. Despite showing statistically significant improvement in overall knowledge, the results did not appear to hold educational significance. Additional POCUS educational methods are necessary to overcome cognitive bias and potential overconfidence. The next stage of curriculum development will include resident-led POCUS workshops to supplement simulation., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
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- 2023
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38. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.
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Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, and Coskun T
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- Adult, Female, Humans, Male, Middle Aged, Blood Glucose, Double-Blind Method, Glucagon therapeutic use, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor therapeutic use, Glucagon-Like Peptides adverse effects, Glucose, Hypoglycemic Agents adverse effects, Receptors, Glucagon therapeutic use, Treatment Outcome, Adolescent, Young Adult, Aged, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 complications
- Abstract
Background: According to current consensus guidelines for type 2 diabetes management, bodyweight management is as important as attaining glycaemic targets. Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a phase 1 study. We aimed to examine the efficacy and safety of retatrutide in people with type 2 diabetes across a range of doses., Methods: In this randomised, double-blind, double-dummy, placebo-controlled and active comparator-controlled, parallel-group, phase 2 trial, participants were recruited from 42 research and health-care centres in the USA. Adults aged 18-75 years with type 2 diabetes, glycated haemoglobin (HbA
1c ) of 7·0-10·5% (53·0-91·3 mmol/mol), and BMI of 25-50 kg/m2 were eligible for enrolment. Eligible participants were treated with diet and exercise alone or with a stable dose of metformin (≥1000 mg once daily) for at least 3 months before the screening visit. Participants were randomly assigned (2:2:2:1:1:1:1:2) using an interactive web-response system, with stratification for baseline HbA1c and BMI, to receive once-weekly injections of placebo, 1·5 mg dulaglutide, or retatrutide maintenance doses of 0·5 mg, 4 mg (starting dose 2 mg), 4 mg (no escalation), 8 mg (starting dose 2 mg), 8 mg (starting dose 4 mg), or 12 mg (starting dose 2 mg). Participants, study site personnel, and investigators were masked to treatment allocation until after study end. The primary endpoint was change in HbA1c from baseline to 24 weeks, and secondary endpoints included change in HbA1c and bodyweight at 36 weeks. Efficacy was analysed in all randomly assigned, except inadvertently enrolled, participants, and safety was assessed in all participants who received at least one dose of study treatment. The study is registered at ClinicalTrials.gov, NCT04867785., Findings: Between May 13, 2021, and June 13, 2022, 281 participants (mean age 56·2 years [SD 9·7], mean duration of diabetes 8·1 years [7·0], 156 [56%] female, and 235 [84%] White) were randomly assigned and included in the safety analysis (45 in the placebo group, 46 in the 1·5 mg dulaglutide group, and 47 in the retatrutide 0·5 mg group, 23 in the 4 mg escalation group, 24 in the 4 mg group, 26 in the 8 mg slow escalation group, 24 in the 8 mg fast escalation group, and 46 in the 12 mg escalation group). 275 participants were included in the efficacy analyses (one each in the retatrutide 0·5 mg group, 4 mg escalation group, and 8 mg slow escalation group, and three in the 12 mg escalation group were inadvertently enrolled). 237 (84%) participants completed the study and 222 (79%) completed study treatment. At 24 weeks, least-squares mean changes from baseline in HbA1c with retatrutide were -0·43% (SE 0·20; -4·68 mmol/mol [2·15]) for the 0·5 mg group, -1·39% (0·14; -15·24 mmol/mol [1·56]) for the 4 mg escalation group, -1·30% (0·22; -14·20 mmol/mol [2·44]) for the 4 mg group, -1·99% (0·15; -21·78 mmol/mol [1·60]) for the 8 mg slow escalation group, -1·88% (0·21; -20·52 mmol/mol [2·34]) for the 8 mg fast escalation group, and -2·02% (0·11; -22·07 mmol/mol [1·21]) for the 12 mg escalation group, versus -0·01% (0·21; -0·12 mmol/mol [2·27]) for the placebo group and -1·41% (0·12; -15·40 mmol/mol [1·29]) for the 1·5 mg dulaglutide group. HbA1c reductions with retatrutide were significantly greater (p<0·0001) than placebo in all but the 0·5 mg group and greater than 1·5 mg dulaglutide in the 8 mg slow escalation group (p=0·0019) and 12 mg escalation group (p=0·0002). Findings were consistent at 36 weeks. Bodyweight decreased dose dependently with retatrutide at 36 weeks by 3·19% (SE 0·61) for the 0·5 mg group, 7·92% (1·28) for the 4 mg escalation group, 10·37% (1·56) for the 4 mg group, 16·81% (1·59) for the 8 mg slow escalation group, 16·34% (1·65) for the 8 mg fast escalation group, and 16·94% (1·30) for the 12 mg escalation group, versus 3·00% (0·86) with placebo and 2·02% (0·72) with 1·5 mg dulaglutide. For retatrutide doses of 4 mg and greater, decreases in weight were significantly greater than with placebo (p=0·0017 for the 4 mg escalation group and p<0·0001 for others) and 1·5 mg dulaglutide (all p<0·0001). Mild-to-moderate gastrointestinal adverse events, including nausea, diarrhoea, vomiting, and constipation, were reported in 67 (35%) of 190 participants in the retatrutide groups (from six [13%] of 47 in the 0·5 mg group to 12 [50%] of 24 in the 8 mg fast escalation group), six (13%) of 45 participants in the placebo group, and 16 (35%) of 46 participants in the 1·5 mg dulaglutide group. There were no reports of severe hypoglycaemia and no deaths during the study., Interpretation: In people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists. These phase 2 data also informed dose selection for the phase 3 programme., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests JR has received grants and research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Novartis, Novo Nordisk, Pfizer, and Sanofi; served on scientific advisory boards and received honorarium or consulting fees from Applied Therapeutics, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Terns Pharma, and Zealand; received honorarium for lectures or educational events from Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, and Sanofi; and received support for attending meetings or travel from Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, and Sanofi. AMJ has received grants and contracts (paid to their institution) from Novo Nordisk, Eli Lilly and Company, Rhythm Pharmaceutical, and the US National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; consults for Amgen and Scholar Rock; has received honoraria or travel expenses from Eli Lilly and Company, Novo Nordisk, and WeightWatchers; has stock options from Intellihealth; and serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly and Company, Intellihealth, Novo Nordisk, Rhythm Pharmaceuticals, Structure Therapeutics, Terns Pharmaceuticals, and WeightWatchers. JF reports research funding from Akero, AstraZeneca, Boehringer Ingelheim, 89bio, Eli Lilly and Company, Intercept, IONIS, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxel, and Sanofi; consulting fees from Akero, Altimmune, Boehringer Ingelheim, Carmot Therapeutics, Echosens, 89bio, Eli Lilly and Company, Merck, Novo Nordisk, Pfizer, and Sanofi; speaker bureau fees from Eli Lilly and Company; support for attending meetings or travel from Eli Lilly and Company, Novo Nordisk, Pfizer, and Sanofi; participation on advisory boards and consulting for Altimmune, Becton Dickenson, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly and Company, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, and Sanofi; and is on the Board of Directors of T1D Exchange. YD, JL, SG, MKT, MLH, AH, ZM, and TC are employees and shareholders of Eli Lilly and Company. MKT also reports roles as Industry Chair, Steering Committee for Accelerating Medicines Partnership-Type 2 Diabetes and Steering Committee Member for Accelerating Medicines Partnership-Common Metabolic Diseases., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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39. Medical Mistrust Among Food Insecure Individuals in Appalachia.
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Thomas MK, Amstutz C, Orr-Roderick D, Horter J, and Holben DH
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- Humans, Cross-Sectional Studies, Appalachian Region, Food Insecurity, Trust, Food Supply
- Abstract
This study focused on the relationship between food insecurity and medical mistrust within Appalachia. Food insecurity has negative consequences on health, while medical mistrust can lead to a decrease in health care use, creating additive consequences to already vulnerable populations. Medical mistrust has been defined in various ways, with measures addressing health care organizations and individual health care providers. To determine whether food insecurity has an additive impact on medical mistrust, a cross-sectional survey was completed by 248 residents in Appalachia Ohio while attending community or mobile clinics, food banks, or the county health department. More than one-quarter of the respondents had high levels of mistrust toward health care organizations. Those with high food insecurity levels were more likely to have higher levels of medical mistrust than those with lower levels of food insecurity. Individuals with higher self-identified health issues and older participants had higher medical mistrust scores. Screening for food insecurity in primary care can reduce the impact of mistrust on patient adherence and health care access by increasing patient-centered communication. These findings present a unique perspective on how to identify and mitigate medical mistrust within Appalachia and call attention to the need for further research on the root causes among food insecure residents., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)
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- 2023
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40. The Combined Effect of Delirium and Falls on Length of Stay and Discharge.
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Kalivas B, Zhang J, Harper K, Dulin J, Heincelman M, Marsden J, Hunt KJ, Mauldin PD, Moran WP, and Thomas MK
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- Humans, Length of Stay, Cross-Sectional Studies, Hospitalization, Retrospective Studies, Patient Discharge, Delirium
- Abstract
Introduction: Delirium or a fall are associated with many negative outcomes including increased length of stay (LOS) and discharge to a facility; however, this relationship is incompletely understood., Methods: A cross-sectional study of all hospitalizations in a large, tertiary care hospital evaluated the effect of delirium and a fall on the outcomes of LOS and risk of being discharged to a facility., Results: The study included 29,655 hospital admissions. A total of 3,707 (12.5%) patients screened positive for delirium and 286 (0.96%) had a reported fall. After adjustment for covariates, relative to patients without delirium or a fall, patients with delirium only had a 1.64-fold longer LOS; patients with fall only had a 1.96-fold longer LOS; and patients who had delirium and fall had a 2.84-fold longer LOS. The adjusted odds of discharge to a facility, relative to those without delirium or a fall, was 8.98 times higher in those with delirium and a fall., Conclusions: Delirium and falls influence LOS and likelihood of being discharged to a facility. The joint impact of falls and delirium on LOS and facility discharge was more than additive. Hospitals should consider the integrated management of delirium and falls., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 National Association for Healthcare Quality.)
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- 2023
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41. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes.
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Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, Mather KJ, Karanikas CA, Dunn J, Haupt A, Milicevic Z, and Coskun T
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- Humans, Obesity complications, Body Weight, Energy Intake, Double-Blind Method, Appetite, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 complications
- Abstract
Objective: To evaluate the effects of tirzepatide on body composition, appetite, and energy intake to address the potential mechanisms involved in body weight loss with tirzepatide., Research Design and Methods: In a secondary analysis of a randomized, double-blind, parallel-arm study, the effects of tirzepatide 15 mg (N = 45), semaglutide 1 mg (N = 44), and placebo (N = 28) on body weight and composition, appetite, and energy intake were assessed at baseline and week 28., Results: Tirzepatide treatment demonstrated significant reductions in body weight compared with placebo and semaglutide, resulting in greater fat mass reduction. Tirzepatide and semaglutide significantly reduced appetite versus placebo. Appetite scores and energy intake reductions did not differ between tirzepatide and semaglutide., Conclusions: Differences in energy intake during ad libitum lunch were not sufficient to explain the different weight outcomes. Further evaluation is needed to assess mechanistic differences related to tirzepatide actions on 24-h energy intake, substrate utilization, and energy expenditure., (© 2023 by the American Diabetes Association.)
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- 2023
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42. SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.
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Schneider EW, Thomas MK, Recchia FM, Reichstein DA, and Awh CC
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- Humans, Angiogenesis Inhibitors, Prospective Studies, Treatment Outcome, Visual Acuity, Receptors, Vascular Endothelial Growth Factor therapeutic use, Recombinant Fusion Proteins therapeutic use, Intravitreal Injections, Macular Degeneration drug therapy, Wet Macular Degeneration diagnosis, Wet Macular Degeneration drug therapy
- Abstract
Purpose: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD)., Methods: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52., Results: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (-31.9 µ m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 µ m compared with week 14. By week 52, improvements in BCVA and CST were lost., Conclusion: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained., Competing Interests: Conflict of Interest(s): E. W. Schneider: Consultant, Carl Zeiss Meditec; Grant Support, Regeneron, Investigator, Genentech, Kodiak Sciences, RegenxBio. M. K. Thomas: None. F. M. Recchia: Speaker, Genentech, Investigator, Genentech, Kodiak Sciences, RegenxBio. D. A. Reichstein: Investigator, Genentech, Kodiak Sciences, RegenxBio. C. C. Awh: Consultant, Genentech, Grant Support, Regeneron; Investigator, Genentech, Kodiak Sciences, RegenxBio.
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- 2023
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43. Tirzepatide as Monotherapy Improved Markers of Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes (SURPASS-1).
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Lee CJ, Mao H, Thieu VT, Landó LF, and Thomas MK
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Context: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes (T2D). SURPASS-1, a phase 3 trial of tirzepatide monotherapy in people with early T2D, enables evaluating effects of tirzepatide on pancreatic beta-cell function and insulin sensitivity (IS) without other background antihyperglycemic medications., Objective: Explore changes in biomarkers of beta-cell function and IS with tirzepatide monotherapy., Design: Post hoc analyses of fasting biomarkers with analysis of variance and mixed model repeated measures., Setting: Forty-seven sites in 4 countries., Patients: Four hundred seventy-eight T2D participants., Intervention: Tirzepatide (5, 10, 15 mg), placebo., Main Outcome Measures: Analyze biomarkers of beta-cell function and IS at 40 weeks., Results: At 40 weeks, markers of beta-cell function improved with tirzepatide monotherapy vs placebo with reductions from baseline in fasting proinsulin levels (49-55% vs -0.6%) and in intact proinsulin/C-peptide ratios (47-49% vs -0.1%) ( P < .001, all doses vs placebo). Increases from baseline in homeostatic model assessment for beta-cell function (computed with C-peptide) (77-92% vs -1.4%) and decreases in glucose-adjusted glucagon levels (37-44% vs +4.8%) were observed with tirzepatide vs placebo ( P < .001, all doses vs placebo). IS improved as indicated by reductions from baseline in homeostatic model assessment for insulin resistance (9-23% vs +14.7%) and fasting insulin levels (2-12% vs +15%), and increases in total adiponectin (16-23% vs -0.2%) and insulin-like growth factor binding protein 2 (38-70% vs +4.1%) with tirzepatide vs placebo at 40 weeks ( P ≤ .031, all doses vs placebo, except for fasting insulin levels with tirzepatide 10 mg)., Conclusions: As monotherapy for early T2D, tirzepatide achieved significant improvements in biomarkers of both pancreatic beta-cell function and IS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2023
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44. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits.
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Costanzo MC, von Grotthuss M, Massung J, Jang D, Caulkins L, Koesterer R, Gilbert C, Welch RP, Kudtarkar P, Hoang Q, Boughton AP, Singh P, Sun Y, Duby M, Moriondo A, Nguyen T, Smadbeck P, Alexander BR, Brandes M, Carmichael M, Dornbos P, Green T, Huellas-Bruskiewicz KC, Ji Y, Kluge A, McMahon AC, Mercader JM, Ruebenacker O, Sengupta S, Spalding D, Taliun D, Smith P, Thomas MK, Akolkar B, Brosnan MJ, Cherkas A, Chu AY, Fauman EB, Fox CS, Kamphaus TN, Miller MR, Nguyen L, Parsa A, Reilly DF, Ruetten H, Wholley D, Zaghloul NA, Abecasis GR, Altshuler D, Keane TM, McCarthy MI, Gaulton KJ, Florez JC, Boehnke M, Burtt NP, and Flannick J
- Subjects
- Humans, Access to Information, Prospective Studies, Genomics methods, Phenotype, Diabetes Mellitus, Type 2 genetics
- Abstract
Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results., Competing Interests: Declaration of interests A.C. is a Sanofi employee and holds shares and stock options in the company. M.I.M. has served on advisory panels for Pfizer, Novo Nordisk, and Zoe Global; has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly; and received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, M.I.M. is an employee of Genentech and a holder of Roche stock. M.R.M. is a Pfizer employee and holds shares of stock in the company. M.K.T. is an employee and shareholder of Eli Lilly and Company. As of April 2022, P.D. is an employee and stockholder of Regeneron Pharmaceuticals., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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45. Considerations for Enteric Disease Surveillance in a Post-COVID-19 Pandemic World: A Canadian Perspective.
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Dougherty B, Smith CR, Forrest RO, Morton V, Sherk LM, Avery B, Kearney A, Christianson S, Nadon C, and Thomas MK
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- Humans, Pandemics, Canada epidemiology, COVID-19 epidemiology
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- 2023
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46. Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease.
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Powell NR, Liang T, Ipe J, Cao S, Skaar TC, Desta Z, Qian HR, Ebert PJ, Chen Y, Thomas MK, and Chalasani N
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- Humans, Cytochrome P-450 CYP2C19 genetics, Cytochrome P-450 CYP2C19 metabolism, Liver metabolism, Liver Cirrhosis pathology, Biopsy, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA expression of genes mediating drug disposition (pharmacogenes) across the histological NAFLD severity spectrum. We utilize RNA-seq for 93 liver biopsies with histologically staged NAFLD Activity Score (NAS), fibrosis stage, and steatohepatitis (NASH). We identify 37 significant pharmacogene-NAFLD severity associations including CYP2C19 downregulation. We chose to validate CYP2C19 due to its actionability in drug prescribing. Meta-analysis of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, to 58% in high NAS, and to 43% in severe fibrosis. Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized medicine approaches for drugs sensitive to metabolism by the CYP2C19 enzyme., (© 2023. The Author(s).)
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- 2023
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47. Impact of the COVID-19 Pandemic on the Reported Incidence of Select Bacterial Enteric Diseases in Canada, 2020.
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Dougherty B, Forrest RO, Smith CR, Morton V, Sherk LM, Avery B, Kearney A, Christianson S, Nadon C, and Thomas MK
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- Humans, Incidence, Pandemics, Communicable Disease Control, Salmonella, Canada epidemiology, COVID-19 epidemiology, Bacterial Infections epidemiology, Shigella, Shiga-Toxigenic Escherichia coli genetics, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology
- Abstract
The aim of this study was to describe the impact of the COVID-19 pandemic on reported cases and clusters of select enteric diseases in Canada, for the period of March 2020 to December 2020. Weekly counts of laboratory confirmed cases of Salmonella , Shigella , Shiga toxin-producing Escherichia coli (STEC), and Listeria monocytogenes were obtained from laboratory surveillance data. These data were supplemented with epidemiological information on the suspected source of illness, collected for cases identified within whole genome sequencing clusters. Incidence rate ratios were calculated for each pathogen. All data were compared with a prepandemic reference period. Decreases in the number of reported cases in 2020 compared with the previous 5-year period were noted for Salmonella , Shigella , Escherichia coli O157, and non-O157 STEC. Reported number of cases for L. monocytogenes in 2020 remained similar to those of the previous 5-year period. There was a considerable decline (59.9%) in the number of cases associated with international travel compared with a 10% decline in the number of domestic cases. Comparison of reported incidence rates of clustered versus sporadic cases for each pathogen showed little variation. This study represents the first formal assessment of the impact of COVID-19 on reported enteric diseases in Canada. Reported case counts across several pathogens saw notable declines in 2020 compared with prepandemic levels, with restrictions on international travel playing a key role. Additional research is needed to understand how limitations on social gatherings, lock downs, and other public health measures have impacted enteric diseases.
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- 2023
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48. The Association between Delirium and In-Hospital Falls: A Cross-Sectional Analysis of a Delirium Screening Program.
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Kalivas B, Zhang J, Harper K, Thomas MK, Dulin J, Marsden J, Robbins P, Hunt KJ, Mauldin PD, Moran WP, Rudolph J, and Heincelman M
- Abstract
Methods: A cross-sectional study using delirium screening and falls reports was used to measure the association between delirium and falls. All inpatient data from August, 2018, to January, 2020, at a large academic medical center were analyzed. A multivariable logistic regression of 29,655 hospital admissions was used to understand the association between in-hospital delirium and falls., Results: Analysis revealed a delirium rate of 12.5% ( n = 3,707) of all admissions and 286 (0.9%) admissions with falls; of the falls studied, 37.6% of these patients screened positive for delirium during their admission. Relative to those who screened negative for delirium, admissions that screened positive for delirium had a 2.81 increased odds of falling., Conclusions: Delirium and falls are related. This strong association should motivate health systems to look closely at both problems. Falls and delirium can both have immense impacts on the patient and the health system. The powerful association between them provides a window to reduce these additional patient harms. More specifically, a modern delirium screening tool should be used as part of routine risk assessment focused on reducing in-hospital falls., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2023 Benjamin Kalivas et al.)
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- 2023
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49. Understanding the association between admission source and in-hospital delirium: A cross-sectional study.
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Thomas MK, Heincelman ME, Zhang J, Marsden J, Dulin J, Robbins P, Hunt K, Mauldin P, Moran WP, and Kalivas B
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- Adult, Humans, Cross-Sectional Studies, Hospitals, Patient Transfer, Emergency Service, Hospital, Length of Stay, Hospitalization, Delirium epidemiology, Delirium diagnosis
- Abstract
Patients admitted via interhospital transfer (IHT) experience increased risk-adjusted mortality, adverse events, length of stay, and discharge to facility; however, the etiology is not well understood. We hypothesize that IHTs are more likely to experience in-hospital delirium as compared with admissions to the hospital via the emergency department (ED) and clinic. This is a cross-sectional study of all adult admissions to medical, surgical, neurological, and obstetrics and gynecology services at an academic medical center who were screened for delirium between August 2018 and January 2020. Unit of analysis was admission source (IHT vs ED vs clinic) as the independent variable and the primary outcome was in-hospital delirium, assessed with initial brief confusion assessment method (bCAM) screening. 30,100 hospitalizations were included in this study with 3925 admissions (13.0%) screening positive for delirium at the initial bCAM assessment. The prevalence of delirium was much higher in IHTs at 22.3% (1334/5971) when compared with clinic at 5.8% (244/4214) and ED at 11.8% (2347/19,915) admissions. Multivariable logistic regression adjusting for demographics and comorbidities showed that IHT admissions had higher odds (OR 1.91, 95% CI 1.74 to 2.10) and clinic admissions had lower odds (OR 0.56, 95% CI 0.48 to 0.64) of in-hospital delirium compared with ED admissions. Increased odds of delirium in IHT admissions may contribute to the observed increased length of stay, discharge to facility, and mortality. These results emphasize the importance of routine screening and possible intervention prior to patient transfer.
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- 2023
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50. A Comparison of Peel-Induced Maculopathy Following ILM Peeling Using a Microvacuum Pick Versus Forceps.
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Thomas AS, Thomas MK, Davis EC, Fowler S, Schneider EW, Recchia FM, and Awh CC
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- Humans, Vitrectomy adverse effects, Vitrectomy methods, Retina, Basement Membrane surgery, Tomography, Optical Coherence, Retrospective Studies, Epiretinal Membrane surgery, Retinal Diseases diagnosis, Retinal Diseases etiology, Retinal Diseases surgery, Macular Degeneration surgery
- Abstract
Objective: To compare peel-induced maculopathy (PIM) using surgical forceps versus the microvacuum pick (MVP)., Methods: Consecutive eyes undergoing internal limiting membrane (ILM) peeling using either the MVP or forceps were assessed. En face optical coherence tomography (OCT) images at the level of the nerve fiber layer were generated for 6-month postoperative visit. The percentage of the imaged area showing PIM was termed the PIM index. PIM severity was additionally measured using a qualitative PIM severity scale., Results: Seventy-four consecutive eyes underwent ILM peeling with either the MVP (36/74; 49%) or forceps (38/74; 51%). At month-6 postoperatively, the mean PIM index for forceps was 7.7% vs 4.7% for the MVP ( P < 0.001, R
2 = 0.15). At 6 months, 26/38 eyes (68.5%) in the forceps group had either moderate or severe PIM compared to 12/36 eyes (33.3%) in the MVP group ( P = 0.001)., Conclusions: ILM peeling with the MVP resulted in lower PIM severity compared to forceps. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:37-42.] .- Published
- 2023
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