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1. Development of text messages for primary prevention of cardiovascular disease in persons with HIV

Author

McLaughlin, Megan M, Hsue, Priscilla Y, Lowe, Dylan A, Olgin, Jeffrey E, and Beatty, Alexis L

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Public Health, Health Sciences, Heart Disease, Behavioral and Social Science, HIV/AIDS, Prevention, Clinical Research, Cardiovascular, Good Health and Well Being, Atherosclerotic cardiovascular disease, Pri-mary prevention, Digital health, Mobile health, Text messages, Hu-man immunodeficiency virus, Human immunodeficiency virus, Primary prevention
Abstract

ObjectivePersons with HIV (PWH) have increased risk for atherosclerotic cardiovascular disease (CVD). Despite this increased risk, perceived cardiovascular risk among PWH is low, and interventions that are known to be beneficial in the general population, such as statins, have low uptake in this population. We sought to develop a bank of text messages about (1) the association between HIV and CVD and (2) advice on reducing cardiovascular risk.MethodsWe developed an initial bank of 162 messages. We solicited feedback from 29 PWH recruited from outpatient clinics providing HIV care at a large urban tertiary medical center and a public hospital in San Francisco, California. Participants reviewed 7-10 messages each and rated message usefulness, readability, and potential impact on behavior on a scale from 1 (least) to 5 (most). We also collected open-ended feedback on the messages and data on preferences about message timing.ResultsThe average score for the messages was 4.4/5 for usefulness, 4.4/5 for readability, and 4.0/5 for potential impact on behavior. The text messages were iteratively revised based on participant feedback, and lowest-rated messages were removed from the message bank. The final message bank included 116 messages on diet (30.2%), physical activity (24.8%), tobacco (11.2%), the association between HIV and cardiovascular disease (9.5%), general heart health (6.9%), cholesterol (5.2%), blood pressure (4.3%), blood sugar (2.6%), sleep (2.6%), and weight (2.6%).ConclusionWe describe an approach for developing educational text messages on primary prevention of cardiovascular disease among PWH.

Published
2023

10. GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus

Author

Levy, Cynthia, primary, Kendrick, Stuart, additional, Bowlus, Christopher L., additional, Tanaka, Atsushi, additional, Jones, David, additional, Kremer, Andreas E., additional, Mayo, Marlyn J., additional, Haque, Nazneen, additional, von Maltzahn, Robyn, additional, Allinder, Matthew, additional, Swift, Brandon, additional, McLaughlin, Megan M., additional, and Hirschfield, Gideon M., additional

Published
2022
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11. Pharmacokinetics and ADME Characterization of Intravenous and Oral [14C]-Linerixibat in Healthy Male Volunteers

Author

Zamek-Gliszczynski, Maciej J., primary, Kenworthy, David, additional, Bershas, David A., additional, Sanghvi, Mitesh, additional, Pereira, Adrian I., additional, Mudunuru, Jennypher, additional, Crossman, Lee, additional, Pirhalla, Jill L., additional, Thorpe, Karl M., additional, Dennison, Jeremy M.T.J., additional, McLaughlin, Megan M., additional, Allinder, Matthew, additional, Swift, Brandon, additional, O’Connor-Semmes, Robin L., additional, and Young, Graeme C., additional

Published
2021
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12. The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants

Author

Sousa, Silvino, McLaughlin, Megan M., Pereira, Sarita A., VanHorn, Stephanie, Knowlton, Robert, Brown, James R., Nicholas, Richard O., and Livi, George P.

Subjects
Microbiological research -- Analysis, Phosphates -- Physiological aspects, Aromatic compounds -- Physiological aspects, Catalysts -- Physiological aspects, Amino acids -- Physiological aspects, Fungi -- Genetic aspects, Prokaryotes -- Genetic aspects, DNA -- Genetic aspects, Cloning -- Genetic aspects, Biological sciences
Abstract

Research has been conducted on 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) which catalyzes aromatic amino acid biosynthesis's first step in prokaryotes, fungi and plants. The cloning of the complete gene defined by the small genomic DNA fragment and the determination of its evolutionary relationship to the DAHP synthases have been carried out and the details are reported.

Published
2002

16. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis

Author

Lee, John C., Laydon, Jeffrey T., McDonnell, Peter C., Gallagher, Timothy F., Kumar, Sanjay, Green, David, McNulty, Dean, Blumenthal, Mary Jane, Heys, J. Richard, Landvatter, Scott W., Strickler, James E., McLaughlin, Megan M., Siemens, Ivo R., Fisher, Seth M., Livi, George P., White, John R., Adams, Jerry L., and Young, Peter R.

Subjects
Protein kinases -- Research, Cytokines -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Radiolabelled and radio-photoaffinity-labelled chemical probes identify the molecular target of pyridinyl-imidazole cytokine inhibitors to be the nitrogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole cytokine inhibitors suppresses the kinase activity of CSBP. This suppression leads to inhibition of cytokine biosynthesis, confirming the crucial role of CSBPs in inflammatory cytokine production.

Published
1994

17. Lp-PLA activity is associated with increased risk of diabetic retinopathy:a longitudinal disease progression study

Author

Siddiqui, Moneeza K, Kennedy, Gwen, Carr, Fiona, Doney, Alexander S F, Pearson, Ewan R, Morris, Andrew D, Johnson, Toby, McLaughlin, Megan M, Williams, Rachel E, and Palmer, Colin N A

Subjects
Journal Article, lipids (amino acids, peptides, and proteins)
Abstract

AIMS/HYPOTHESIS: The aim of the study was to examine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity levels and incident diabetic retinopathy and change in retinopathy grade.METHODS: This was a cohort study of diabetic participants with serum collected at baseline and routinely collected diabetic retinal screening data. Participants with type 2 diabetes from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) cohort were used. This cohort is composed of individuals of white Scottish ancestry from the Tayside region of Scotland. Survival analysis accounting for informative censoring by modelling death as a competing risk was performed for the development of incident diabetic retinopathy from a disease-free state in a 3 year follow-up period (n = 1364) by stratified Lp-PLA2 activity levels (in quartiles). The same analysis was performed for transitions to more severe grades.RESULTS: The hazard of developing incident diabetic retinopathy was 2.08 times higher (95% CI 1.64, 2.63) for the highest quartile of Lp-PLA2 activity compared with the lowest. Higher Lp-PLA2 activity levels were associated with a significantly increased risk for transitions to all grades. The hazards of developing observable (or more severe) and referable (or more severe) retinopathy were 2.82 (95% CI 1.71, 4.65) and 1.87 (95% CI 1.26, 2.77) times higher for the highest quartile of Lp-PLA2 activity compared with the lowest, respectively.CONCLUSIONS/INTERPRETATION: Higher Lp-PLA2 levels are associated with increased risk of death and the development of incident diabetic retinopathy, as well as transitions to more severe grades of diabetic retinopathy. These associations are independent of calculated LDL-cholesterol and other traditional risk factors. Further, this biomarker study shows that the association is temporally sensitive to the proximity of the event to measurement of Lp-PLA2.

Published
2018

19. Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study

Author

Tucker, Joseph D, Cheng, Yu, Wong, Bonnie, Gong, Ni, Nie, Jing-Bao, Zhu, Wei, McLaughlin, Megan M, Xie, Ruishi, Deng, Yinghui, Huang, Meijin, Wong, William CW, Lan, Ping, Liu, Huanliang, Miao, Wei, Kleinman, Arthur, and Patient-Physician Trust Project Team

Subjects
health care economics and organizations
Abstract

OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China. DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships. RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.

Published
2015

20. Impact of itch on quality of life in people with primary biliary cholangitis: A plain language summary

Author

Mayo, Marlyn J, Carey, Elizabeth, Smith, Helen T, Mospan, Andrea R, McLaughlin, Megan M, Thompson, April, Morris, Heather L, Sandefur, Robert A, Bowlus, Christopher L, and Levy, Cynthia

Abstract

What is this summary about?This is a summary of an article about people with primary biliary cholangitis (PBC) who also suffer from itch. PBC is a disease that affects the liver; itching is common in PBC and can dramatically reduce a person's quality of life.People in a study called TARGET-PBC filled in surveys about their PBC symptoms, including itching, and the effects the symptoms had on their lives. Information was also collected on the medications people were taking for their PBC and itch.What were the results?Out of 211 people with PBC who filled in the surveys, 170 (81%) had itching. More than one-third of them (37%) had itch that was clinically significant. Clinically significant itch has been defined as an itch that sometimes affects a person's sleep, makes them scratch until their skin is raw, or causes embarrassment. These people would benefit from a discussion about treatment options. Clinically significant itch was linked with worse scores on the surveys, meaning poorer quality of life. This link was true for all areas looked at, but particularly for social aspects and cognition, such as memory and concentration. Sleep was affected in most people with clinically significant itch and there were high levels of fatigue.People with clinically significant itch were more likely to be taking anti-itch medication compared with those with mild itch, but onethird of them still had not received any treatment for itch. When itch medication was used, the stepwise guidelines suggested by specialty professional societies was not usually followed.What do the results mean?Itching is problematic for the people in this study. Those with clinically significant itch have a worse quality of life compared with those with mild itch and this affects all areas of their life measured. The study also shows that people do not always receive medication for their itch, and that treatment guidelines are not always followed.

Published
2024
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21. Post-hoc analyses of darapladib, an oral Lp-PLA(2) inhibitor, in phase III cardiovascular outcomes trials may inform investigation in diabetic macular edema

Author

Williams, Rachel, Shearn, Shawn Patrick, Dowd, Michael, Cicconetti, Greg, Wallentin, Lars, White, Harvey, Janmohamed, Salim, Wurzelmann, John I., McLaughlin, Megan M., Williams, Rachel, Shearn, Shawn Patrick, Dowd, Michael, Cicconetti, Greg, Wallentin, Lars, White, Harvey, Janmohamed, Salim, Wurzelmann, John I., and McLaughlin, Megan M.

Published
2015

22. Lp-PLA2 activity is associated with increased risk of diabetic retinopathy: a longitudinal disease progression study.

Author

Siddiqui, Moneeza K., Kennedy, Gwen, Carr, Fiona, Doney, Alexander S. F., Pearson, Ewan R., Morris, Andrew D., Johnson, Toby, McLaughlin, Megan M., Williams, Rachel E., and Palmer, Colin N. A.

Abstract

Aims/hypothesis: The aim of the study was to examine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) activity levels and incident diabetic retinopathy and change in retinopathy grade.Methods: This was a cohort study of diabetic participants with serum collected at baseline and routinely collected diabetic retinal screening data. Participants with type 2 diabetes from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) cohort were used. This cohort is composed of individuals of white Scottish ancestry from the Tayside region of Scotland. Survival analysis accounting for informative censoring by modelling death as a competing risk was performed for the development of incident diabetic retinopathy from a disease-free state in a 3 year follow-up period (n = 1364) by stratified Lp-PLA2 activity levels (in quartiles). The same analysis was performed for transitions to more severe grades.Results: The hazard of developing incident diabetic retinopathy was 2.08 times higher (95% CI 1.64, 2.63) for the highest quartile of Lp-PLA2 activity compared with the lowest. Higher Lp-PLA2 activity levels were associated with a significantly increased risk for transitions to all grades. The hazards of developing observable (or more severe) and referable (or more severe) retinopathy were 2.82 (95% CI 1.71, 4.65) and 1.87 (95% CI 1.26, 2.77) times higher for the highest quartile of Lp-PLA2 activity compared with the lowest, respectively.Conclusions/interpretation: Higher Lp-PLA2 levels are associated with increased risk of death and the development of incident diabetic retinopathy, as well as transitions to more severe grades of diabetic retinopathy. These associations are independent of calculated LDL-cholesterol and other traditional risk factors. Further, this biomarker study shows that the association is temporally sensitive to the proximity of the event to measurement of Lp-PLA2. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Cloning, Expression, and Initial Characterization of a Novel Cytokine-like Gene Family

Author

Zhu, Yuan, primary, Xu, Gang, additional, Patel, Arun, additional, McLaughlin, Megan M., additional, Silverman, Carol, additional, Knecht, Kristin A., additional, Sweitzer, Sharon, additional, Li, Xiaotong, additional, McDonnell, Peter, additional, Mirabile, Rosanna, additional, Zimmerman, Dawn, additional, Boyce, Rogely, additional, Tierney, Lauren A., additional, Hu, Erding, additional, Livi, George P., additional, Wolf, Bryan A., additional, Abdel-Meguid, Sherin S., additional, Rose, George D., additional, Aurora, Rejeev, additional, Hensley, Preston, additional, Briggs, Michael, additional, and Young, Peter R., additional

Published
2002
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34. Temperature-sensitive Differential Affinity of TRAIL for Its Receptors

Author

Truneh, Alemseged, primary, Sharma, Sunita, additional, Silverman, Carol, additional, Khandekar, Sanjay, additional, Reddy, Manjula P., additional, Deen, Keith C., additional, Mclaughlin, Megan M., additional, Srinivasula, Srinivasa M., additional, Livi, George P., additional, Marshall, Lisa A., additional, Alnemri, Emad S., additional, Williams, William V., additional, and Doyle, Michael L., additional

Published
2000
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35. A G Protein-coupled Receptor for UDP-glucose

Author

Chambers, Jon K., primary, Macdonald, Lynn E., additional, Sarau, Henry M., additional, Ames, Robert S., additional, Freeman, Katie, additional, Foley, James J., additional, Zhu, Yuan, additional, McLaughlin, Megan M., additional, Murdock, Paul, additional, McMillan, Lynette, additional, Trill, John, additional, Swift, Ann, additional, Aiyar, Nambi, additional, Taylor, Paul, additional, Vawter, Lisa, additional, Naheed, Sajda, additional, Szekeres, Philip, additional, Hervieu, Guillaume, additional, Scott, Claire, additional, Watson, Jeanette M., additional, Murphy, Andrew J., additional, Duzic, Emir, additional, Klein, Christine, additional, Bergsma, Derk J., additional, Wilson, Shelagh, additional, and Livi, George P., additional

Published
2000
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36. Acquisition of Sensitivity of Stress-activated Protein Kinases to the p38 Inhibitor, SB 203580, by Alteration of One or More Amino Acids within the ATP Binding Pocket

Author

Gum, Rebecca J., primary, McLaughlin, Megan M., additional, Kumar, Sanjay, additional, Wang, Zhulun, additional, Bower, Michael J., additional, Lee, John C., additional, Adams, Jerry L., additional, Livi, George P., additional, Goldsmith, Elizabeth J., additional, and Young, Peter R., additional

Published
1998
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37. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site

Author

Young, Peter R., primary, McLaughlin, Megan M., additional, Kumar, Sanjay, additional, Kassis, Shouki, additional, Doyle, Michael L., additional, McNulty, Dean, additional, Gallagher, Timothy F., additional, Fisher, Seth, additional, McDonnell, Peter C., additional, Carr, Steven A., additional, Huddleston, Michael J., additional, Seibel, George, additional, Porter, Terence G., additional, Livi, George P., additional, Adams, Jerry L., additional, and Lee, John C., additional

Published
1997
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38. Autocatalytic Activation of Human Cathepsin K

Author

McQueney, Michael S., primary, Amegadzie, Bernard Y., additional, D'Alessio, Karla, additional, Hanning, Charles R., additional, McLaughlin, Megan M., additional, McNulty, Dean, additional, Carr, Steven A., additional, Ijames, Carl, additional, Kurdyla, Jeff, additional, and Jones, Christopher S., additional

Published
1997
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45. The tyrosine89 residue of yeast FKBP12 is required for rapamycin binding

Author

Koser, Paul L, primary, Eng, Wai-Kwong, additional, Bossard, Mary J, additional, McLaughlin, Megan M, additional, Cafferkey, Robert, additional, Sathe, Ganesh M, additional, Faucette, Leo, additional, Levy, Mark A, additional, Johnson, Randall K, additional, Bergsma, Derk J, additional, and Livi, George P, additional

Published
1993
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47. The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence

Author

Koser, Paul L., primary, Bergsma, Derk J., additional, Cafferkey, Robert, additional, Eng, Wai-Kwong, additional, McLaughlin, Megan M., additional, Ferrara, Anne, additional, Silverman, Carol, additional, Kasyan, Karla, additional, Bossard, Mary J., additional, Johnson, Randall K., additional, Porter, Terence G., additional, Levy, Mark A., additional, and Livi, George P., additional

Published
1991
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49. Mixed-Strain Mycobacterium tuberculosisInfections and the Implications for Tuberculosis Treatment and Control

Author

Cohen, Ted, van Helden, Paul D., Wilson, Douglas, Colijn, Caroline, McLaughlin, Megan M., Abubakar, Ibrahim, and Warren, Robin M.

Abstract

SUMMARYNumerous studies have reported that individuals can simultaneously harbor multiple distinct strains of Mycobacterium tuberculosis. To date, there has been limited discussion of the consequences for the individual or the epidemiological importance of mixed infections. Here, we review studies that documented mixed infections, highlight challenges associated with the detection of mixed infections, and discuss possible implications of mixed infections for the diagnosis and treatment of patients and for the community impact of tuberculosis control strategies. We conclude by highlighting questions that should be resolved in order to improve our understanding of the importance of mixed-strain M. tuberculosisinfections.

Published
2012
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50. Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

Author

Hedt-Gauthier, Bethany, Atwood, Sidney S., Omotayo, David B., Ntlamelle, Likhapha, Satti, Hind Elkheir, Seung, Kwonjune Justin, and McLaughlin, Megan M

Subjects
Medicine, Global Health, Infectious Diseases, Bacterial Diseases, Tuberculosis, Multi-Drug-Resistant Tuberculosis, Sexually Transmitted Diseases, AIDS, Tropical Diseases (Non-Neglected), Viral Diseases, HIV, HIV diagnosis and management, HIV epidemiology, Non-Clinical Medicine, Health Care Providers, Public Health, Behavioral and Social Aspects of Health
Abstract

Background: Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure. Methods: We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes. Results: Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52). Conclusions: Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.

Published
2012
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