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1. Educational Intervention Among Adolescents and Young Adults on Emergency Contraception Options.

Author

Harper, Cynthia C, Jones, Erin, Brindis, Claire D, Watson, Annalisa, Schroeder, Rosalyn, Boyer, Cherrie B, Edelman, Alison, Trieu, Sang, and Yarger, Jennifer

Subjects
Humans, Levonorgestrel, Contraception, Contraception, Postcoital, Odds Ratio, Intrauterine Devices, Intrauterine Devices, Copper, Awareness, Adolescent, Adult, Female, Male, Young Adult, Adolescent and young adult contraceptive knowledge, Emergency contraception, Emergency contraceptive pills, IUD for emergency contraception, Levonorgestrel emergency contraceptive pills, Ulipristal acetate, Clinical Research, Adolescent Sexual Activity, Pediatric, Good Health and Well Being, Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Public Health
Abstract

PurposeEmergency contraception (EC), the 'last chance' contraceptive method, has gained significance post-Roe, but most young people do not know their options.MethodsWe conducted an educational intervention on EC among 1,053 students aged 18-25 years. We assessed changes in knowledge of key aspects of EC using generalized estimating equations.ResultsAt baseline, virtually no one was aware of the intrauterine device for EC (4%), but postintervention, 89% correctly identified intrauterine devices as the most effective EC (adjusted odds ratio [aOR] = 116.6; 95% confidence interval [CI] 62.4, 217.8). Knowledge that levonorgestrel pills could be accessed without a prescription grew (60%-90%; aOR = 9.7, 95% CI 6.7-14.0), as did knowledge that pills work best when taken as soon as possible (75%-95%; aOR = 9.6, 95% CI 6.1-14.9). Multivariate results showed adolescent and young adult participants absorbed these key concepts across age, gender, and sexual orientation.DiscussionTimely interventions are needed to empower youth with knowledge of EC options.

Published
2023

2. Germline mutations in penetrant cancer predisposition genes are rare in men with prostate cancer selecting active surveillance

Author

Brady, Lauren, Newcomb, Lisa F, Zhu, Kehao, Zheng, Yingye, Boyer, Hilary, De Sarkar, Navonil, McKenney, Jesse K, Brooks, James D, Carroll, Peter R, Dash, Atreya, Ellis, William J, Filson, Christopher P, Gleave, Martin E, Liss, Michael A, Martin, Frances, Morgan, Todd M, Thompson, Ian M, Wagner, Andrew A, Pritchard, Colin C, Lin, Daniel W, and Nelson, Peter S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Cancer, Prostate Cancer, Genetics, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Male, Humans, Germ-Line Mutation, Watchful Waiting, Retrospective Studies, Prostatic Neoplasms, Genes, BRCA2, Genetic Predisposition to Disease, active surveillance, adverse pathology, germline mutations, prostate cancer, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

BackgroundPathogenic germline mutations in several rare penetrant cancer predisposition genes are associated with an increased risk of aggressive prostate cancer (PC). Our objectives were to determine the prevalence of pathogenic germline mutations in men with low-risk PC on active surveillance, and assess whether pathogenic germline mutations associate with grade reclassification or adverse pathology, recurrence, or metastases, in men treated after initial surveillance.MethodsMen prospectively enrolled in the Canary Prostate Active Surveillance Study (PASS) were retrospectively sampled for the study. Germline DNA was sequenced utilizing a hereditary cancer gene panel. Mutations were classified according to the American College of Clinical Genetics and Genomics' guidelines. The association of pathogenic germline mutations with grade reclassification and adverse characteristics was evaluated by weighted Cox proportional hazards modeling and conditional logistic regression, respectively.ResultsOverall, 29 of 437 (6.6%) study participants harbored a pathogenic germline mutation of which 19 occurred in a gene involved in DNA repair (4.3%). Eight participants (1.8%) had pathogenic germline mutations in three genes associated with aggressive PC: ATM, BRCA1, and BRCA2. The presence of pathogenic germline mutations in DNA repair genes did not associate with adverse characteristics (univariate analysis HR = 0.87, 95% CI: 0.36-2.06, p = 0.7). The carrier rates of pathogenic germline mutations in ATM, BRCA1, and BRCA2did not differ in men with or without grade reclassification (1.9% vs. 1.8%).ConclusionThe frequency of pathogenic germline mutations in penetrant cancer predisposition genes is extremely low in men with PC undergoing active surveillance and pathogenic germline mutations had no apparent association with grade reclassification or adverse characteristics.

Published
2022

3. Analysis of separate training and validation radical prostatectomy cohorts identifies 0.25 mm diameter as an optimal definition for "large" cribriform prostatic adenocarcinoma.

Author

Chan, Emily, McKenney, Jesse K, Hawley, Sarah, Corrigan, Dillon, Auman, Heidi, Newcomb, Lisa F, Boyer, Hilary D, Carroll, Peter R, Cooperberg, Matthew R, Klein, Eric, Fazli, Ladan, Gleave, Martin E, Hurtado-Coll, Antonio, Simko, Jeffry P, Nelson, Peter S, Thompson, Ian M, Tretiakova, Maria S, Troyer, Dean, True, Lawrence D, Vakar-Lopez, Funda, Lin, Daniel W, Brooks, James D, Feng, Ziding, and Nguyen, Jane K

Subjects
Humans, Adenocarcinoma, Prostatic Neoplasms, Prostatectomy, Retrospective Studies, Male, Neoplasm Grading, Clinical Research, Cancer, Medical and Health Sciences, Pathology
Abstract

Cribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests "large" cribriform glands associate with aggressive behavior; however, published studies use varying definitions for "large". We aimed to identify an outcome-based quantitative cut-off for "large" vs "small" cribriform glands. We conducted an initial training phase using the tissue microarray based Canary retrospective radical prostatectomy cohort. Of 1287 patients analyzed, cribriform growth was observed in 307 (24%). Using Kaplan-Meier estimates of recurrence-free survival curves (RFS) that were stratified by cribriform gland size, we identified 0.25 mm as the optimal cutoff to identify more aggressive disease. In univariable and multivariable Cox proportional hazard analyses, size >0.25 mm was a significant predictor of worse RFS compared to patients with cribriform glands ≤0.25 mm, independent of pre-operative PSA, grade, stage and margin status (p 0.25 mm had a significantly lower RFS relative to patients with cribriform glands ≤0.25 mm (each subset p = 0.004). Furthermore, there was no significant difference in outcomes between patients with cribriform glands ≤ 0.25 mm and patients without cribriform glands. The >0.25 mm cut-off was validated as statistically significant in a separate 419 patient, completely embedded whole-section radical prostatectomy cohort by biochemical recurrence, metastasis-free survival, and disease specific death, even when cases with admixed Gleason pattern 5 carcinoma were excluded. In summary, our findings support reporting cribriform gland size and identify 0.25 mm as an optimal outcome-based quantitative measure for defining "large" cribriform glands. Moreover, cribriform glands >0.25 mm are associated with potential for metastatic disease independent of Gleason pattern 5 adenocarcinoma.

Published
2022

4. Serum Lateral Flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two-centre mixed cohort study.

Author

Hoenigl, Martin, Egger, Matthias, Boyer, Johannes, Schulz, Eduard, Prattes, Juergen, and Jenks, Jeffrey D

Subjects
Bronchoalveolar Lavage Fluid, Humans, Aspergillus, Mannans, Antigens, Fungal, Diagnostic Tests, Routine, Immunoassay, Sensitivity and Specificity, Retrospective Studies, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Invasive Pulmonary Aspergillosis, Young Adult, Automation, Laboratory, Aspergillus galactomannan Lateral Flow assay, COVID-19, HIV, SARS-CoV2, galactomannan, haematologic malignancy, intensive care unit, respiratory diseases, serum, solid organ transplant recipients, Clinical Research, Rare Diseases, Microbiology, Clinical Sciences
Abstract

BackgroundDetection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients.MethodsWe performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics.ResultsIn total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non-classifiable (n = 94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p

Published
2021

5. Mental Health and Psychosocial Risk and Protective Factors Among Black and Latinx Transgender Youth Compared With Peers

Author

Vance, Stanley Ray, Boyer, Cherrie B, Glidden, David V, and Sevelius, Jae

Subjects
Public Health, Health Sciences, Mental Health, Behavioral and Social Science, Pediatric, Sexual and Gender Minorities (SGM/LGBT*), Prevention, Depression, Good Health and Well Being, Adolescent, Black or African American, Female, Health Surveys, Hispanic or Latino, Humans, Male, Mental Disorders, Peer Group, Prevalence, Protective Factors, Retrospective Studies, Risk Factors, Transgender Persons, United States, Young Adult, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceBlack and Latinx transgender youth experience stigma that may increase their susceptibility to mental health symptoms.ObjectiveTo compare past-year mental health symptoms and psychosocial factors among Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth.Design, setting, and participantsThis survey study used data from the 2015-2017 Biennial California Healthy Kids Survey with a weighted sample (N = 45 269) representative of California's secondary school population. The analytic sample (n = 19 780) included Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth in the 9th and 11th grades. Data analysis was conducted from July 2020 to February 2021.Main outcomes and measuresOutcomes include past-year depressive symptoms and suicidality. Psychosocial risk factors include school-based victimization, gender-based harassment, sexuality-based harassment, and race-based harassment; protective factors include school connectedness and caring adult relationships.ResultsThe analytic sample of 19 780 participants (in 9th grade: weighted percentage, 51% [95% CI, 50% to 52%]; female participants: weighted percentage, 50% [95% CI, 49% to 51%]) included 252 Black and Latinx transgender youth (weighted percentage, 1.3% [95% CI, 1.1% to 1.5%]), 104 White transgender youth (weighted percentage, 0.7% [95% CI, 0.6% to 0.8%]), and 19 424 Black and Latinx cisgender youth (weighted percentage, 98.0% [95% CI, 97.8% to 98.2%]). For Black and Latinx transgender youth, estimated prevalence of depressive symptoms and suicidality were 50% (95% CI, 44% to 57%) and 46% (95% CI, 39% to 52%), respectively. Logistic regression models adjusted for grade, living arrangement, and reported sex indicated that compared with White transgender youth, Black and Latinx transgender youth had similar odds of depressive symptoms (adjusted odds ratio, 0.6; 95% CI, 0.4 to 1.1) and suicidality (adjusted odds ratio, 1.1; 95% CI, 0.6 to 1.8) and similar odds of all forms of harassment (eg, race-based harassment: adjusted odds ratio, 1.5; 95% CI, 0.8 to 2.6). Regression models indicated that compared with White transgender youth, Black and Latinx transgender youth had similar levels of victimization (adjusted linear regression coefficient, 0.5; 95% CI, -0.3 to 1.3) and caring adult relationships (adjusted linear regression coefficient, -0.6; 95% CI, -1.4 to 0.09) but lower levels of school connectedness (adjusted linear regression coefficient, -1.6; 95% CI, -2.9 to -0.4). With similar analyses, compared with Black and Latinx cisgender youth, Black and Latinx transgender youth had higher odds of depressive symptoms (adjusted odds ratio, 2.7; 95% CI, 2.0 to 3.7) and suicidality (adjusted odds ratio, 5.9; 95% CI, 4.3 to 8.0), higher odds and levels of all forms of harassment and victimization (eg, race-based harassment: adjusted odds ratio, 3.2; 95% CI, 2.4 to 4.5), and lower levels of school connectedness (adjusted linear regression coefficient, -2.6; 95% CI -3.3 to -1.8) and caring adult relationships (adjusted linear regression coefficient, -0.9; 95% CI -1.3 to -0.5).Conclusions and relevanceIn this study, Black and Latinx transgender youth had high rates of mental health symptoms, with rates comparable with White transgender youth but higher than Black and Latinx cisgender youth. Their unique pattern of psychosocial risk and protective factors for these mental health symptoms should be factored in clinical preventive services and school-based interventions to support them.

Published
2021

6. Magnetic Resonance Imaging for the Detection of High Grade Cancer in the Canary Prostate Active Surveillance Study.

Author

Liss, Michael A, Newcomb, Lisa F, Zheng, Yingye, Garcia, Michael P, Filson, Christopher P, Boyer, Hilary, Brooks, James D, Carroll, Peter R, Cooperberg, Matthew R, Ellis, William J, Gleave, Martin E, Martin, Frances M, Morgan, Todd, Nelson, Peter S, Wagner, Andrew A, Thompson, Ian M, and Lin, Daniel W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Clinical Research, Cancer, Urologic Diseases, Prevention, Aging, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Aged, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Grading, Prospective Studies, Prostatic Neoplasms, Watchful Waiting, prostatic neoplasms, magnetic resonance imaging, Urology & Nephrology, Clinical sciences
Abstract

PurposeWe investigated the ability of prostate magnetic resonance imaging to detect Gleason Grade Group 2 or greater cancer in a standardized, multi-institutional active surveillance cohort.Materials and methodsWe evaluated men enrolled in Canary Prostate Active Surveillance Study with Gleason Grade Group less than 2 and who underwent biopsy within 12 months of multiparametric magnetic resonance imaging. Our primary outcome was biopsy reclassification to Gleason Grade Group 2 or greater. We evaluated the performance of magnetic resonance imaging PI-RADS® score and clinical factors. Multivariable logistic regression models were fit with magnetic resonance imaging and clinical factors and used to perform receiver operating curve analyses.ResultsThere were 361 participants with 395 prostate magnetic resonance imaging studies with a median followup of 4.1 (IQR 2.0-7.6) years. Overall 108 (27%) biopsies showed reclassification. Defining positive magnetic resonance imaging as PI-RADS 3-5, the negative predictive value and positive predictive value for detecting Gleason Grade Group 2 or greater cancer was 83% (95% CI 76-90) and 31% (95% CI 26-37), respectively. PI-RADS was significantly associated with reclassification (PI-RADS 5 vs 1 and 2 OR 2.71, 95% CI 1.21-6.17, p=0.016) in a multivariable model but did not improve upon a model with only clinical factors (AUC 0.768 vs 0.762). In 194 fusion biopsies higher grade cancer was found in targeted cores in 21 (11%) instances, while 25 (13%) had higher grade cancer in the systematic cores.ConclusionsThis study adds the largest cohort data to the body of literature for magnetic resonance imaging in active surveillance, recommending systematic biopsy in patients with negative magnetic resonance imaging and the inclusion of systematic biopsy in patients with positive magnetic resonance imaging.

Published
2020

7. Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial

Author

Esquenazi, Alberto, Stoquart, Gaëtan, Hedera, Peter, Jacinto, Luis Jorge, Dimanico, Ugo, Constant‐Boyer, Francois, Brashear, Allison, Grandoulier, Anne‐Sophie, Vilain, Claire, Picaut, Philippe, and Gracies, Jean‐Michel

Subjects
Health Sciences, Sports Science and Exercise, Infectious Diseases, Clinical Research, Emerging Infectious Diseases, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Botulinum Toxins, Type A, Double-Blind Method, Female, Humans, Lower Extremity, Male, Middle Aged, Muscle Spasticity, Neuromuscular Agents, Paresis, Treatment Outcome, Young Adult, Clinical Sciences, Clinical sciences, Allied health and rehabilitation science
Abstract

ObjectiveTo examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA.DesignSecondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study.SettingFifty-two centers (11 countries).PatientsAdults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb.Main outcome measurementsMuscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented.ResultsOf 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA.ConclusionsPatients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

Published
2020

8. Misclassification of sexual health risks in a self-identified low risk cohort of men who have sex with men (MSM) enrolled in a community based PrEP program

Author

Freeborn, Kellie, Portillo, Carmen, Boyer, Cherie B, and Santos, Glen Milo

Subjects
Public Health, Health Sciences, HIV/AIDS, Sexually Transmitted Infections, Pediatric AIDS, Prevention, Clinical Research, Pediatric, Sexual and Gender Minorities (SGM/LGBT*), Infectious Diseases, Behavioral and Social Science, Infection, Good Health and Well Being, Adult, Anti-HIV Agents, Cohort Studies, Community Health Services, Condoms, HIV Infections, Homosexuality, Male, Humans, Longitudinal Studies, Male, Mass Screening, Middle Aged, Pre-Exposure Prophylaxis, Risk Factors, Risk-Taking, Safe Sex, San Francisco, Sexual Health, Sexually Transmitted Diseases, Unsafe Sex, Young Adult, MSM, risk perception, PrEP, Public Health and Health Services, Psychology, Public health, Sociology, Clinical and health psychology
Abstract

The CDC recommends PrEP for MSM at substantial risk of HIV acquisition, leaving clinicians unsure whether to prescribe PrEP to MSM who do not disclose HIV risk factors. A longitudinal cohort of MSM requesting PrEP despite reporting during a clinical visit either 100% condom use or participation in oral sex only and no other risk factors was followed over 13 months at a community clinic in San Francisco to assess the accuracy of their HIV risk perception. Participants completed a sexual and substance use behavior questionnaire at baseline, outside of the clinical visit and were followed by quarterly HIV/STI testing and condom use change questionnaires. Condomless sex increased from 0% at baseline to 12% at month 1, peaked at 34% at month 7, and then decreased again to 8% at month 13. Rates of pharyngeal GC/CT varied from 7% at baseline to 12% at month 13, while rectal GC/CT decreased from 6% at baseline to 0% at month 13. The rate of syphilis was 1% both at baseline and at month 13, however, 11% and 15% of clients tested positive for syphilis at months 1 and 7 respectively.

Published
2020

9. Multivalvular Endocarditis Involving 3 Valves in a Nonsurgical Candidate

Author

Boyer, Robin, Grandhe, Sundeep, Win, Theingi, Ragland, Alan, and Heidari, Arash

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Heart Disease, Infectious Diseases, Rare Diseases, Clinical Research, Good Health and Well Being, Anti-Bacterial Agents, Embolism, Endocarditis, Bacterial, Heart Valves, Humans, Male, Middle Aged, Streptococcus mutans, Treatment Outcome, endocarditis, emboli, management, trivalvular, multivalvular
Abstract

Infective endocarditis is associated with high morbidity and mortality. Hence, early diagnosis and prompt intervention is crucial. Multivalvular endocarditis involving 3 or more valves is rarely reported with little information regarding best management or prognosis, particularly in nonsurgical patients. Conflicting guidelines regarding medical versus surgical treatment in multivalvular endocarditis exist with few studies describing the outcome of medically managed patients. We report the case of a previously healthy male presenting with infective endocarditis involving 3 valves further complicated by multiple septic emboli and deemed a nonsurgical candidate.

Published
2020

10. Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair

Author

Ma, Jianhui, Benitez, Jorge A, Li, Jie, Miki, Shunichiro, de Albuquerque, Claudio Ponte, Galatro, Thais, Orellana, Laura, Zanca, Ciro, Reed, Rachel, Boyer, Antonia, Koga, Tomoyuki, Varki, Nissi M, Fenton, Tim R, Marie, Suely Kazue Nagahashi, Lindahl, Erik, Gahman, Timothy C, Shiau, Andrew K, Zhou, Huilin, DeGroot, John, Sulman, Erik P, Cavenee, Webster K, Kolodner, Richard D, Chen, Clark C, and Furnari, Frank B

Subjects
Genetics, Rare Diseases, Brain Disorders, Cancer, Neurosciences, Brain Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Animals, Brain Neoplasms, Cell Nucleus, DNA Repair, Female, Glioma, Humans, Male, Mice, PTEN Phosphohydrolase, Phosphorylation, Pyrimidines, Rad51 Recombinase, Radiation Tolerance, Receptor, Fibroblast Growth Factor, Type 2, Tyrosine, Xenograft Model Antitumor Assays, DNA damage, FGFR2, GBM, PTEN, ionizing radiation, tyrosine phosphorylation, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.

Published
2019

11. Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation.

Author

Kabagambe, Sandra K, Palma, Ivonne P, Smolin, Yulia, Boyer, Tristan, Palma, Ivania, Sageshima, Junichiro, Troppmann, Christoph, Santhanakrishnan, Chandrasekar, McVicar, John P, Jen, Kuang-Yu, Nuño, Miriam, and Perez, Richard V

Subjects
Humans, Kidney Transplantation, Hypothermia, Induced, Perfusion, Adult, Aged, Middle Aged, Tissue Donors, Female, Male, Cold Ischemia, Delayed Graft Function, Hypothermia, Induced, Surgery, Medical and Health Sciences
Abstract

BackgroundDespite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation.MethodsFrom June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed.ResultsAfter a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance.ConclusionsFavorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.

Published
2019

12. Persistent Left Superior Vena Cava: Implications of Surgical Management

Author

Boyer, Robin, Sidhu, Ramanjeet, Ghandforoush, Aslan, Win, Theingi, and Heidari, Arash

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Adult, Defibrillators, Implantable, Heart Defects, Congenital, Heart Failure, Heart Transplantation, Humans, Incidental Findings, Male, Vena Cava, Superior, superior vena cava, coronary, transplant, surgical management
Abstract

Persistent left superior vena cava is the most common congenital anomaly of thoracic venous return, which results when the left anterior cardinal vein fails to regress. A 41-year-old African American male with a history of an unspecified childhood cardiac murmur presented to the emergency department with congestive heart failure exacerbation revealing an incidental finding of a persistent left superior vena cava. Ultimately, he required implantable cardioverter defibrillator placement and cardiac transplantation assessment. In the setting of advanced device placement or cardiac transplantation, a persistent left superior vena cava warrants several important clinical considerations at a center capable of addressing the possibility of a right-sided approach and transplantation irregularities.

Published
2019

13. Effectiveness of informational decision aids and a live donor financial assistance program on pursuit of live kidney transplants in African American hemodialysis patients

Author

Boulware, L Ebony, Ephraim, Patti L, Ameling, Jessica, Lewis-Boyer, LaPricia, Rabb, Hamid, Greer, Raquel C, Crews, Deidra C, Jaar, Bernard G, Auguste, Priscilla, Purnell, Tanjala S, Lamprea-Monteleagre, Julio A, Olufade, Tope, Gimenez, Luis, Cook, Courtney, Campbell, Tiffany, Woodall, Ashley, Ramamurthi, Hema, Davenport, Cleomontina A, Choudhury, Kingshuk Roy, Weir, Matthew R, Hanes, Donna S, Wang, Nae-Yuh, Vilme, Helene, and Powe, Neil R

Subjects
Health Services and Systems, Health Sciences, Kidney Disease, Clinical Research, Clinical Trials and Supportive Activities, Renal and urogenital, Adult, Black or African American, Aged, Decision Making, Decision Support Techniques, Female, Financial Support, Health Knowledge, Attitudes, Practice, Humans, Kidney Transplantation, Living Donors, Male, Middle Aged, Patient Participation, Renal Dialysis, Tissue and Organ Procurement, Treatment Outcome, Decision aid, End stage renal disease, Financial support, Live donor kidney transplant Race disparities, Live donor kidney transplant, Race disparities, Clinical Sciences, Urology & Nephrology, Clinical sciences, Health services and systems, Nursing
Abstract

BackgroundAfrican Americans have persistently poor access to living donor kidney transplants (LDKT). We conducted a small randomized trial to provide preliminary evidence of the effect of informational decision support and donor financial assistance interventions on African American hemodialysis patients' pursuit of LDKT.MethodsStudy participants were randomly assigned to receive (1) Usual Care; (2) the Providing Resources to Enhance African American Patients' Readiness to Make Decisions about Kidney Disease (PREPARED); or (3) PREPARED plus a living kidney donor financial assistance program. Our primary outcome was patients' actions to pursue LDKT (discussions with family, friends, or doctor; initiation or completion of the recipient LDKT medical evaluation; or identification of a donor). We also measured participants' attitudes, concerns, and perceptions of interventions' usefulness.ResultsOf 329 screened, 92 patients were eligible and randomized to Usual Care (n = 31), PREPARED (n = 30), or PREPARED plus financial assistance (n = 31). Most participants reported interventions helped their decision making about renal replacement treatments (62%). However there were no statistically significant improvements in LDKT actions among groups over 6 months. Further, no participants utilized the living donor financial assistance benefit.ConclusionsFindings suggest these interventions may need to be paired with personal support or navigation services to overcome key communication, logistical, and financial barriers to LDKT.Trial registrationClinicalTrials.gov [ NCT01439516 ] [August 31, 2011].

Published
2018

14. The mitochondrial calcium uniporter underlies metabolic fuel preference in skeletal muscle

Author

Kwong, Jennifer Q, Huo, Jiuzhou, Bround, Michael J, Boyer, Justin G, Schwanekamp, Jennifer A, Ghazal, Nasab, Maxwell, Joshua T, Jang, Young C, Khuchua, Zaza, Shi, Kevin, Bers, Donald M, Davis, Jennifer, and Molkentin, Jeffery D

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Health Sciences, Sports Science and Exercise, Nutrition, Aetiology, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Musculoskeletal, Metabolic and endocrine, Animals, Calcium, Calcium Channels, Calcium Signaling, Energy Metabolism, Female, Gene Targeting, Male, Mice, Mice, Transgenic, Muscle, Skeletal, Cardiology, Mitochondria, Muscle Biology, Biomedical and clinical sciences, Health sciences
Abstract

The mitochondrial Ca2+ uniporter (MCU) complex mediates acute mitochondrial Ca2+ influx. In skeletal muscle, MCU links Ca2+ signaling to energy production by directly enhancing the activity of key metabolic enzymes in the mitochondria. Here, we examined the role of MCU in skeletal muscle development and metabolic function by generating mouse models for the targeted deletion of Mcu in embryonic, postnatal, and adult skeletal muscle. Loss of Mcu did not affect muscle growth and maturation or otherwise cause pathology. Skeletal muscle-specific deletion of Mcu in mice also did not affect myofiber intracellular Ca2+ handling, but it did inhibit acute mitochondrial Ca2+ influx and mitochondrial respiration stimulated by Ca2+, resulting in reduced acute exercise performance in mice. However, loss of Mcu also resulted in enhanced muscle performance under conditions of fatigue, with a preferential shift toward fatty acid metabolism, resulting in reduced body fat with aging. Together, these results demonstrate that MCU-mediated mitochondrial Ca2+ regulation underlies skeletal muscle fuel selection at baseline and under enhanced physiological demands, which affects total homeostatic metabolism.

Published
2018

15. Structural Effects on HIV Risk Among Youth: A Multi-level Analysis

Author

Miller, Robin Lin, Strzyzykowski, Trevor, Lee, Kyung-Sook, Chiaramonte, Danielle, Acevedo-Polakovich, Ignacio, Spring, Hannah, Santiago-Rivera, Olga, Boyer, Cherrie B, and Ellen, Jonathan M

Subjects
Public Health, Health Sciences, Pediatric AIDS, Prevention, Infectious Diseases, HIV/AIDS, Clinical Research, Pediatric, Behavioral and Social Science, Adolescent Sexual Activity, Infection, Adolescent, Female, HIV Infections, Humans, Male, Multilevel Analysis, Sexual Behavior, Sexual Partners, Sexual and Gender Minorities, Social Stigma, Social Support, Stress, Psychological, United States, Structural stigma, Concentrated disadvantage, HIV risk behavior, High-risk youth, Public Health and Health Services, Social Work, Public health
Abstract

We proposed a multilevel model of structural influences on HIV-risky sexual partnerships in a diverse sample of 1793 youth residing in 23 states and the District of Columbia. We examined the influence of concentrated disadvantage, HIV stigma, and sexual and gender minority stigma on engagement in HIV risky sexual partnerships and whether youth's participation in opportunity structures, anticipation of HIV stigma, and perceptions of their community as youth-supportive settings mediated structural effects. After controlling for age, HIV status, and race, we found structural HIV stigma had deleterious indirect effects on youth's participation in HIV-risky sexual partnerships. Concentrated disadvantage and structural sexual and gender minority stigma had direct negative effects on youth's perceptions of their communities as supportive and on their participation in prosocial activity. Support perceptions had direct, protective effects on avoidance of HIV-risky sexual partnerships. Structural stigma undermines youth's belief that their communities invest in their safety and well-being.

Published
2018

16. Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression

Author

Jacobsohn, David A, Loken, Michael R, Fei, Mingwei, Adams, Alexia, Brodersen, Lisa Eidenschink, Logan, Brent R, Ahn, Kwang Woo, Shaw, Bronwen E, Kletzel, Morris, Olszewski, Marie, Khan, Sana, Meshinchi, Soheil, Keating, Amy, Harris, Andrew, Teira, Pierre, Duerst, Reggie E, Margossian, Steven P, Martin, Paul L, Petrovic, Aleksandra, Dvorak, Christopher C, Nemecek, Eneida R, Boyer, Michael W, Chen, Allen R, Davis, Jeffrey H, Shenoy, Shalini, Savasan, Sureyya, Hudspeth, Michelle P, Adams, Roberta H, Lewis, Victor A, Kheradpour, Albert, Kasow, Kimberly A, Gillio, Alfred P, Haight, Ann E, Bhatia, Monica, Bambach, Barbara J, Haines, Hilary L, Quigg, Troy C, Greiner, Robert J, Talano, Julie-An M, Delgado, David C, Cheerva, Alexandra, Gowda, Madhu, Ahuja, Sanjay, Ozkaynak, Mehmet, Mitchell, David, Schultz, Kirk R, Fry, Terry J, Loeb, David M, and Pulsipher, Michael A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Pediatric, Rare Diseases, Stem Cell Research - Nonembryonic - Human, Clinical Research, Transplantation, Pediatric Research Initiative, Hematology, Regenerative Medicine, Genetics, Stem Cell Research, Cancer, Pediatric Cancer, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Inflammatory and immune system, Adolescent, Adult, Allografts, Child, Child, Preschool, Disease-Free Survival, Female, Flow Cytometry, Hematopoietic Stem Cell Transplantation, Humans, Infant, Infant, Newborn, Leukemia, Myeloid, Acute, Male, Neoplasm, Residual, Transplantation Conditioning, Transplantation, Homologous, Unrelated Donors, WT1 Proteins, Cytogenetics and molecular genetics, Measurable residual disease, Stem cell transplantation, Laboratory hematology, Clinical Sciences, Immunology, Cardiovascular medicine and haematology
Abstract

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.

Published
2018

17. Examination of Behavioral, Social, and Environmental Contextual Influences on Sexually Transmitted Infections in At Risk, Urban, Adolescents, and Young Adults

Author

Boyer, Cherrie B, Santiago Rivera, Olga J, Chiaramonte, Danielle M, and Ellen, Jonathan M

Subjects
Paediatrics, Biomedical and Clinical Sciences, Public Health, Health Sciences, Sexually Transmitted Infections, Behavioral and Social Science, Prevention, Infectious Diseases, Good Health and Well Being, Adolescent, Black or African American, Child, Female, HIV Infections, Homosexuality, Male, Humans, Logistic Models, Male, Prevalence, Self Report, Sex Factors, Sexual Behavior, Sexual Partners, Sexual and Gender Minorities, Sexually Transmitted Diseases, Social Class, Transgender Persons, Young Adult, Biological Sciences, Medical and Health Sciences, Clinical sciences, Epidemiology, Public health
Abstract

BackgroundDespite the large body of extant literature on sexually transmitted infections (STIs) in adolescents and young adults (AYAs), more research on social and environmental contextual factors is needed. Also, further examination of STI indicators by gender remains a critical area of research focus.MethodsAnonymous survey data were collected using audio computer-assisted self-interviews in community venues in urban, low-income, STI prevalent, US neighborhoods to reach AYAs, aged 12 to 24 years. Conventional descriptive statistics, bivariate analysis, and multiple logistical regression models were used to assess indicators of a self-reported lifetime prevalence of STIs.ResultsParticipants (N = 1540) were on average 20.6 years; 57.2% were women, the majority were racial and ethnic minorities (92%), and almost half (49.2%) identified as sexual minorities. Nearly one third (32.%) had 1 or more STIs. As expected, gender differences were identified. For AYA men, being African American/Black, moving residences more than 4 times since kindergarten, and having a history of human immunodeficiency virus testing were each positively associated with STIs. Also, those who strongly disagreed that many young people in their community exchanged sex for money had a significantly lower likelihood of having an STI. For AYA women, exchanging sex for drugs or money, lacking money, which prevented activities, and using marijuana were each associated with STIs.ConclusionsThis research extends our understanding of social and environmental contextual influences on AYAs' risk for STIs. It highlights differences in risk exposures that are distinctly different for AYA women and men, suggesting the need for tailored interventions to address their unique economic needs and social challenges.

Published
2018

18. Linking HIV-Negative Youth to Prevention Services in 12 U.S. Cities: Barriers and Facilitators to Implementing the HIV Prevention Continuum

Author

Doll, Mimi, Fortenberry, J Dennis, Roseland, Denise, McAuliff, Kathleen, Wilson, Craig M, and Boyer, Cherrie B

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Public Health, Health Sciences, Pediatric, Mental Health, Behavioral and Social Science, Prevention, Infectious Diseases, Health Services, Clinical Research, HIV/AIDS, Pediatric AIDS, Adolescent Sexual Activity, 8.1 Organisation and delivery of services, Prevention of disease and conditions, and promotion of well-being, Health and social care services research, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Infection, Good Health and Well Being, Adolescent, HIV Infections, Health Services Accessibility, Humans, Interviews as Topic, Male, Mass Screening, Patient Acceptance of Health Care, Pre-Exposure Prophylaxis, Qualitative Research, Sexual and Gender Minorities, Young Adult, Linkage to prevention, High-risk HIV-negative youth, HIV prevention, HIV prevention infrastructure, YMSM of color, Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

PurposeLinkage of HIV-negative youth to prevention services is increasingly important with the development of effective pre-exposure prophylaxis that complements behavioral and other prevention-focused interventions. However, effective infrastructure for delivery of prevention services does not exist, leaving many programs to address HIV prevention without data to guide program development/implementation. The objective of this study was to provide a qualitative description of barriers and facilitators of linkage to prevention services among high-risk, HIV-negative youth.DesignThematic analysis of structured interviews with staff implementing linkage to prevention services programs for youth aged 12-24 years.MethodsTwelve adolescent medicine HIV primary care programs as part of larger testing research program focused on young sexual minority men of color. The study included staff implementing linkage to prevention services programs along with community-based HIV testing programs. The main outcomes of the study were key barriers/facilitators to linkage to prevention services.ResultsEight themes summarized perspectives on linkage to prevention services: (1) relationships with community partners, (2) trust between providers and youth, (3) youth capacity to navigate prevention services, (4) pre-exposure prophylaxis specific issues, (5) privacy issues, (6) gaps in health records preventing tailored services, (7) confidentiality of care for youth accessing services through parents'/caretakers' insurance, and (8) need for health-care institutions to keep pace with models that prioritize HIV prevention among at-risk youth. Themes are discussed in the context of factors that facilitated/challenged linkage to prevention services.ConclusionsSeveral evidence-based HIV prevention tools are available; infrastructures for coordinated service delivery to high-risk youth have not been developed. Implementation of such infrastructures requires attention to community-, provider-, and youth-related issues.

Published
2018

19. Structural and Community Change Outcomes of the Connect‐to‐Protect Coalitions: Trials and Triumphs Securing Adolescent Access to HIV Prevention, Testing, and Medical Care

Author

Miller, Robin Lin, Reed, Sarah J, Chiaramonte, Danielle, Strzyzykowski, Trevor, Spring, Hannah, Acevedo‐Polakovich, Ignacio D, Chutuape, Kate, Cooper‐Walker, Bendu, Boyer, Cherrie B, and Ellen, Jonathan M

Subjects
Psychology, Clinical and Health Psychology, Social and Personality Psychology, Applied and Developmental Psychology, Pediatric AIDS, Pediatric, Clinical Trials and Supportive Activities, Prevention, HIV/AIDS, Clinical Research, Infection, Good Health and Well Being, Adolescent, Capacity Building, Community Networks, Community Participation, Female, HIV Infections, Health Services Accessibility, Humans, Male, United States, HIV, AIDS, Youth, adolescents, Coalitions, AIDS competence, Structural change, Community capacity, Youth/adolescents, Social Work, Public Health, Applied and developmental psychology, Clinical and health psychology, Social and personality psychology
Abstract

Connect to Protect (C2P), a 10-year community mobilization effort, pursued the dual aims of creating communities competent to address youth's HIV-related risks and removing structural barriers to youth health. We used Community Coalition Action Theory (CCAT) to examine the perceived contributions and accomplishments of 14 C2P coalitions. We interviewed 318 key informants, including youth and community leaders, to identify the features of coalitions' context and operation that facilitated and undermined their ability to achieve structural change and build communities' capability to manage their local adolescent HIV epidemic effectively. We coded the interviews using an a priori coding scheme informed by CCAT and scholarship on AIDS-competent communities. We found community mobilization efforts like C2P can contribute to addressing the structural factors that promote HIV-risk among youth and to community development. We describe how coalition leadership, collaborative synergy, capacity building, and local community context influence coalitions' ability to successfully implement HIV-related structural change, demonstrating empirical support for many of CCAT's propositions. We discuss implications for how community mobilization efforts might succeed in laying the foundation for an AIDS-competent community.

Published
2017

20. Reducing Cancer and Cancer Disparities: Lessons From a Youth-Generated Diabetes Prevention Campaign.

Author

Schillinger, Dean, Ling, Pamela M, Fine, Sarah, Boyer, Cherrie B, Rogers, Elizabeth, Vargas, Roberto Ariel, Bibbins-Domingo, Kirsten, and Chou, Wen-Ying Sylvia

Subjects
Humans, Neoplasms, Diabetes Mellitus, Obesity, Health Knowledge, Attitudes, Practice, Adolescent Behavior, Health Behavior, Social Behavior, Health Education, Minority Groups, Schools, Marketing, Social Marketing, Mass Media, Adolescent, Adult, Health Promotion, Female, Male, Health Status Disparities, Young Adult, Health Communication, Social Media, Tobacco Use, Health Knowledge, Attitudes, Practice, Pediatric, Cancer, Prevention, Pediatric Research Initiative, Behavioral and Social Science, 3.1 Primary prevention interventions to modify behaviours or promote well-being, Public Health, Medical and Health Sciences, Education
Abstract

Adolescence and young adulthood, a period essential for determining exposures over the life-course, is an ideal time to intervene to lower cancer risk. This demographic group can be viewed as both the target audience and generator of messages for cancer prevention, such as skin cancer, obesity-, tobacco-, and human papillomavirus-related cancers. The purpose of this paper is to encourage innovative health communications that target youth; youth behavior; and the structural, environmental, and social determinants of youth behavior as critical areas of focus for cancer prevention and disparities reduction. The authors describe the rationale, processes, products, and early impacts of an award-winning youth diabetes prevention communication campaign model (The Bigger Picture) that harnesses spoken-word messages in school-based and social media presentations. The campaign supports minority adolescent and young adult artists to create content that aligns with values held closely by youth-values likely to resonate and affect change, such as defiance against authority, inclusion, and social justice. This campaign can be leveraged to prevent obesity, which is a cancer risk factor. Then, the authors propose concrete ways that The Bigger Picture's pedagogical model could be adapted for broader cancer prevention messaging for youth of color and youth stakeholders regarding tobacco-related cancers, skin cancers, and human papillomavirus-related cancers. The goal is to demonstrate how a youth-generated and youth-targeted prevention campaign can: (1) reframe conversations about cancer prevention, (2) increase awareness that cancer prevention is about social justice and health equity, and (3) catalyze action to change social norms and confront the social and environmental drivers of cancer disparities.

Published
2017

21. Evaluating Testing Strategies for Identifying Youths With HIV Infection and Linking Youths to Biomedical and Other Prevention Services

Author

Miller, Robin Lin, Boyer, Cherrie B, Chiaramonte, Danielle, Lindeman, Peter, Chutuape, Kate, Cooper-Walker, Bendu, Kapogiannis, Bill G, Wilson, Craig M, and Fortenberry, J Dennis

Subjects
Pediatric, Adolescent Sexual Activity, Infectious Diseases, Behavioral and Social Science, Pediatric AIDS, Clinical Research, Prevention, HIV/AIDS, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adolescent, Adolescent Health Services, African Americans, Community Health Centers, Continuity of Patient Care, HIV Infections, Humans, Male, Mass Screening, Patient Acceptance of Health Care, Program Evaluation, Sexual and Gender Minorities, United States, Young Adult, Black or African American, Paediatrics and Reproductive Medicine, Pediatrics
Abstract

ImportanceMost human immunodeficiency virus (HIV)-infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical.ObjectiveTo evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results.Design, setting, and participantsTesting strategies were evaluated using an observational design during a 9-month period (June 1, 2015, through February 28, 2016). Testing strategies were implemented by 12 adolescent medicine HIV primary care programs and included targeted testing, universal testing, or a combination. Data were collected from local youth at high risk of HIV infection and, specifically, sexual minority males of color.Main outcomes and measuresProportion of sexual minority males and sexual minority males of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of linkage to prevention services.ResultsA total of 3301 youths underwent HIV testing. Overall, 35 (3.6%) of those who underwent universal testing in primary care clinical settings, such as emergency departments and community health centers, were sexual minority males (35 [3.6%] were males of color) compared with 236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted testing and 693 (37.8%) (503 [27.4%] were males of color) through combination efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%) via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%) through targeted testing. However, when targeted tests were separated from universal testing results for sites using a combined strategy, the rate of newly identified HIV-positive cases identified through universal testing decreased to 1 (0.1%). Rates of new HIV-positive cases identified through targeted testing increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%]) were more likely to link successfully to local HIV prevention services, including preexposure prophylaxis, compared with those who underwent universal testing (328 [34.1%]).Conclusions and relevanceThe findings suggest that community-based targeted approaches to HIV testing are more effective than universal screening for reaching young sexual minority males (especially males of color), identifying previously undiagnosed HIV-positive youths, and linking HIV-negative youths to relevant prevention services. Targeted, community-based HIV testing strategies hold promise as a scalable and effective means to identify high-risk youths who are unaware of their HIV status.

Published
2017

22. Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency

Author

Simon, Mariella T, Ng, Bobby G, Friederich, Marisa W, Wang, Raymond Y, Boyer, Monica, Kircher, Martin, Collard, Renata, Buckingham, Kati J, Chang, Richard, Shendure, Jay, Nickerson, Deborah A, Bamshad, Michael J, Genomics, University of Washington Center for Mendelian, Van Hove, Johan LK, Freeze, Hudson H, and Abdenur, Jose E

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Aetiology, 2.1 Biological and endogenous factors, Child, Child, Preschool, Congenital Abnormalities, Gene Expression, Humans, Infant, Infant, Newborn, Male, Mitochondrial Proteins, Oxidative Phosphorylation, Peptide Elongation Factor G, RNA Splice Sites, GFM1, Mitochondrial disease, Congenital disorders of glycosylation, Mitochondrial elongation factor, Cryptic splice site, University of Washington Center for Mendelian Genomics, Biochemistry & Molecular Biology, Biochemistry and cell biology
Abstract

We report the clinical, biochemical, and molecular findings in two brothers with encephalopathy and multi-systemic disease. Abnormal transferrin glycoforms were suggestive of a type I congenital disorder of glycosylation (CDG). While exome sequencing was negative for CDG related candidate genes, the testing revealed compound heterozygous mutations in the mitochondrial elongation factor G gene (GFM1). One of the mutations had been reported previously while the second, novel variant was found deep in intron 6, activating a cryptic splice site. Functional studies demonstrated decreased GFM1 protein levels, suggested disrupted assembly of mitochondrial complexes III and V and decreased activities of mitochondrial complexes I and IV, all indicating combined OXPHOS deficiency.

Published
2017

23. Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context

Author

Boyer, Cherrie B, Greenberg, Lauren, Chutuape, Kate, Walker, Bendu, Monte, Dina, Kirk, Jennifer, Ellen, Jonathan M, and the Adolescent Medicine Trials Network

Subjects
Health Sciences, Public Health, Criminology, Human Society, HIV/AIDS, Behavioral and Social Science, Sexual and Gender Minorities (SGM/LGBT*), Clinical Research, Pediatric, Violence Research, Mental Health, Prevention, Good Health and Well Being, Adolescent, Age Factors, Drug Trafficking, Female, HIV Infections, Humans, Male, Residence Characteristics, Risk Factors, Sex Factors, Sex Work, Sexual and Gender Minorities, Socioeconomic Factors, Substance-Related Disorders, United States, Young Adult, Adolescents and young adults, Exchange of sex, Community context, STI/HIV risk, Adolescent Medicine Trials Network, Public Health and Health Services, Epidemiology, Public health, Development studies
Abstract

The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p

Published
2017

24. A diagnosis of prostate cancer and pursuit of active surveillance is not followed by weight loss: potential for a teachable moment

Author

Liss, MA, Schenk, JM, Faino, AV, Newcomb, LF, Boyer, H, Brooks, JD, Carroll, PR, Dash, A, Fabrizio, MD, Gleave, ME, Nelson, PS, Neuhouser, ML, Wei, JT, Zheng, Y, Wright, JL, Lin, DW, and Thompson, IM

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Urologic Diseases, Prostate Cancer, Cancer, Nutrition, Patient Safety, Prevention, Aging, Obesity, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Body Mass Index, Body Weight, Disease Progression, Humans, Life Style, Male, Middle Aged, Prospective Studies, Prostatic Neoplasms, Risk Factors, Weight Loss, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundObesity is a risk factor for incident prostate cancer (PC) as well as risk of disease progression and mortality. We hypothesized that men diagnosed with lower-risk PC and who elected active surveillance (AS) for their cancer management would likely initiate lifestyle changes that lead to weight loss.MethodsPatients were enrolled in the Prostate Active Surveillance Study (PASS), a multicenter prospective biomarker discovery and validation study of men who have chosen AS for their PC. Data from 442 men diagnosed with PC within 1 year of study entry who completed a standard of care 12-month follow-up visit were analyzed. We examined the change in weight and body mass index (BMI) over the first year of study participation.ResultsAfter 1 year on AS, 7.5% (33/442) of patients had lost 5% or more of their on-study weight. The proportion of men who lost 5% or more weight was similar across categories of baseline BMI: normal/underweight (8%), overweight (6%) and obese (10%, χ2 test P=0.44). The results were similar for patients enrolled in the study 1 year or 6 months after diagnosis. By contrast, after 1 year, 7.7% (34/442) of patients had gained >5% of their weight.ConclusionsOnly 7.5% of men with low-risk PC enrolled in AS lost a modest (⩾5%) amount of weight after diagnosis. Given that obesity is related to PC progression and mortality, targeted lifestyle interventions may be effective at this 'teachable moment', as men begin AS for low-risk PC.

Published
2016

25. Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N‐3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people

Author

Lemas, Dominick J, Klimentidis, Yann C, Aslibekyan, Stella, Wiener, Howard W, O'Brien, Diane M, Hopkins, Scarlett E, Stanhope, Kimber L, Havel, Peter J, Allison, David B, Fernandez, Jose R, Tiwari, Hemant K, and Boyer, Bert B

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Genetics, Obesity, Prevention, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adult, Alaska, Anthropometry, Apolipoprotein A-I, Cholesterol, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diet, Fatty Acids, Omega-3, Female, Glucose Transporter Type 4, Glycated Hemoglobin, Humans, Male, Polymorphism, Single Nucleotide, Stearoyl-CoA Desaturase, Sterol Regulatory Element Binding Protein 1, Alaska Native, BMI, Gene-by-environment interactions, n-3 PUFA, Food Sciences, Public Health and Health Services, Food Science, Nutrition & Dietetics, Food sciences, Nutrition and dietetics
Abstract

Scopen-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes.Materials and methodsAnthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels.ConclusionThe results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people.

Published
2016

26. Increased expression of ApoE and protection from amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA.

Author

Coskun, Pinar, Cáceres-Del-Carpio, Javier, Udar, Nitin, Boyer, David, Jazwinski, S, Miceli, Michael, Nesburn, Anthony, Thaker, Kunal, Chwa, Marilyn, Kuppermann, Baruch, Kenney, Maria, and Atilano, Shari

Subjects
APOE, Amyloid-β(1–42), Complement inhibitors, Cybrids, Epigenetics, Haplogroup, Inflammasome, Mitochondrial DNA, Adult, Aged, Amyloid beta-Peptides, Apolipoproteins E, Cell Nucleus, DNA, Mitochondrial, Female, Haplotypes, Humans, Male, Middle Aged, Mitochondria, Oxidative Phosphorylation, Polymorphism, Single Nucleotide, Reactive Oxygen Species, Signal Transduction, Young Adult
Abstract

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-β peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-β1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-β42-1 (inactive form) (p

Published
2016

27. Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies.

Author

Tretiakova, MS, Wei, W, Boyer, HD, Newcomb, LF, Hawley, S, Auman, H, Vakar-Lopez, F, McKenney, JK, Fazli, L, Simko, J, Troyer, DA, Hurtado-Coll, A, Thompson, IM, Carroll, PR, Ellis, WJ, Gleave, ME, Nelson, PS, Lin, DW, True, LD, Feng, Z, and Brooks, JD

Subjects
Humans, Prostatic Neoplasms, Recurrence, Prostate-Specific Antigen, Ki-67 Antigen, Neoplasm Staging, Prognosis, Prostatectomy, Tissue Array Analysis, Proportional Hazards Models, Cell Proliferation, Male, Kaplan-Meier Estimate, Neoplasm Grading, Cancer, Urologic Diseases, Prostate Cancer, Patient Safety, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Oncology and Carcinogenesis, Urology & Nephrology
Abstract

BackgroundExpanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes.MethodsAfter immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up).ResultsIn 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P

Published
2016

28. Increased expression of ApoE and protection from amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA.

Author

Thaker, Kunal, Chwa, Marilyn, Atilano, Shari R, Coskun, Pinar, Cáceres-Del-Carpio, Javier, Udar, Nitin, Boyer, David S, Jazwinski, S Michal, Miceli, Michael V, Nesburn, Anthony B, Kuppermann, Baruch D, and Kenney, M Cristina

Subjects
Cell Nucleus, Mitochondria, Humans, Reactive Oxygen Species, Apolipoproteins E, DNA, Mitochondrial, Signal Transduction, Oxidative Phosphorylation, Haplotypes, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Young Adult, Amyloid beta-Peptides, APOE, Amyloid-β(1–42), Complement inhibitors, Cybrids, Epigenetics, Haplogroup, Inflammasome, Mitochondrial DNA, Genetics, Aetiology, 2.1 Biological and endogenous factors, Amyloid-beta(1-42), Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-β peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2'-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-β1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-β42-1 (inactive form) (p

Published
2016

29. Creating Youth-Supportive Communities: Outcomes from the Connect-to-Protect® (C2P) Structural Change Approach to Youth HIV Prevention

Author

Miller, Robin Lin, Janulis, Patrick F, Reed, Sarah J, Harper, Gary W, Ellen, Jonathan, and Boyer, Cherrie B

Subjects
Psychology, Clinical and Health Psychology, Social and Personality Psychology, Applied and Developmental Psychology, Behavioral and Social Science, Adolescent Sexual Activity, Prevention, Clinical Research, Pediatric AIDS, HIV/AIDS, Pediatric, Good Health and Well Being, Adolescent, Black or African American, Community Networks, Community-Based Participatory Research, Cross-Sectional Studies, Female, HIV Infections, Hispanic or Latino, Homosexuality, Male, Humans, Male, Sexual Behavior, Social Stigma, Young Adult, HIV prevention, Structural change, Coalitions, High-risk youth, Young MSM, Adolescent Medicine Trials Network for HIV/AIDS Interventions, Specialist Studies in Education, Developmental & Child Psychology, Applied and developmental psychology, Clinical and health psychology, Social and personality psychology
Abstract

Reducing HIV incidence among adolescents represents an urgent global priority. Structural change approaches to HIV prevention may reduce youth risk by addressing the economic, social, cultural, and political factors that elevate it. We assessed whether achievement of structural changes made by eight Connect-to-Protect (C2P) coalitions were associated with improvements in youth's views of their community over the first 4 years of coalitions' mobilization. We recruited annual cross-sectional samples of targeted youth from each C2P community. We sampled youth in neighborhood venues. We interviewed a total of 2461 youth over 4 years. Males (66 %) and youth of color comprised the majority (52 % Hispanic/Latinos; 41 % African Americans) of those interviewed. By year 4, youth reported greater satisfaction with their community as a youth-supportive setting. They reported their needs were better met by available community resources compared with year 1. However, these findings were moderated by risk population such that those from communities where C2P focused on young men who have sex with men (YMSM) reported no changes over time whereas those from communities focused on other at-risk youth reported significant improvements over time in satisfaction and resource needs being met. Internalized HIV stigma increased over time among those from communities serving other at-risk youth and was unchanged among those from YMSM communities. The very different results we observe over time between communities focused on YMSM versus other at-risk youth may suggest it is unreasonable to assume identical chains of structural causality across youth populations who have such different historical relationships to HIV and who encounter very different kinds of entrenched discrimination within their communities.

Published
2016

30. Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort.

Author

Newcomb, Lisa F, Thompson, Ian M, Boyer, Hilary D, Brooks, James D, Carroll, Peter R, Cooperberg, Matthew R, Dash, Atreya, Ellis, William J, Fazli, Ladan, Feng, Ziding, Gleave, Martin E, Kunju, Priya, Lance, Raymond S, McKenney, Jesse K, Meng, Maxwell V, Nicolas, Marlo M, Sanda, Martin G, Simko, Jeffry, So, Alan, Tretiakova, Maria S, Troyer, Dean A, True, Lawrence D, Vakar-Lopez, Funda, Virgin, Jeff, Wagner, Andrew A, Wei, John T, Zheng, Yingye, Nelson, Peter S, Lin, Daniel W, and Canary PASS Investigators

Subjects
Canary PASS Investigators, Humans, Prostatic Neoplasms, Biopsy, Treatment Outcome, Prostatectomy, Tumor Burden, Population Surveillance, Risk Factors, Prospective Studies, Aged, Middle Aged, Male, Watchful Waiting, Neoplasm Grading, Biomarkers, Tumor, prospective studies, prostatic neoplasms, watchful waiting, Clinical Research, Urologic Diseases, Prostate Cancer, Cancer, Prevention, Aging, Patient Safety, Clinical Sciences, Urology & Nephrology
Abstract

PurposeActive surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multicenter study of active surveillance.Materials and methodsWe studied 905 men in the prospective Canary PASS enrolled between 2008 and 2013. We collected clinical data at study entry and at prespecified intervals, and determined associations with adverse reclassification, defined as increased Gleason grade or greater cancer volume on followup biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance.ResultsAt a median followup of 28 months 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued on active surveillance. Overall 19% of participants received treatment, 68% with adverse reclassification, while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling the percent of biopsy cores with cancer, body mass index and prostate specific antigen density were associated with adverse reclassification (p=0.01, 0.04, 0.04, respectively). Of 103 participants subsequently treated with radical prostatectomy 34% had adverse pathology, defined as primary pattern 4-5 or nonorgan confined disease, including 2 with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (p=0.76).ConclusionsMost men remain on active surveillance at 5 years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only a modest association with disease reclassification, supporting the need for approaches that improve the prediction of this outcome.

Published
2016

31. Targeting Structural Change for HIV Prevention

Author

Willard, Nancy, Chutuape, Kate, Stewart-Campbell, Rachel, Boyer, Cherrie B, and Ellen, Jonathan

Subjects
Public Health, Health Sciences, HIV/AIDS, Clinical Trials and Supportive Activities, Prevention, Infectious Diseases, Clinical Research, Infection, Good Health and Well Being, Acquired Immunodeficiency Syndrome, Adolescent, Capacity Building, Community Networks, Cooperative Behavior, Female, HIV Infections, Health Education, Health Services Accessibility, Housing, Humans, Male, Mental Health Services, Residence Characteristics, Risk Assessment, United States, Urban Population, Young Adult, structural change and HIV, strategic planning, HIV prevention, coalition capacity building, Public Health and Health Services, Curriculum and Pedagogy, Public health
Abstract

To address the persistent HIV epidemic in the United States, prevention efforts are focusing on social determinants related to HIV risk by targeting systems and structures, such as organizational and institutional policies, practices and programs, and legislative and regulatory approaches to modify features of the environment that influence HIV risk. With limited evidenced-based examples, communities can benefit from strategic planning resources that help them consider developing structural-level changes that target root causes of HIV risk. In this article, we present the Connect to Protect® project that outlines a process and a tool to move from general ideas to specific structural changes. Examples from 14 coalitions are also provided. Using the process and tools presented here can provide a launching pad for other coalitions seeking to build an HIV prevention agenda and for practitioners seeking to incorporate structural changes for community health promotion.

Published
2015

32. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder

Author

Mertens, Jerome, Wang, Qiu-Wen, Kim, Yongsung, Yu, Diana X, Pham, Son, Yang, Bo, Zheng, Yi, Diffenderfer, Kenneth E, Zhang, Jian, Soltani, Sheila, Eames, Tameji, Schafer, Simon T, Boyer, Leah, Marchetto, Maria C, Nurnberger, John I, Calabrese, Joseph R, Oedegaard, Ketil J, McCarthy, Michael J, Zandi, Peter P, Alda, Martin, Nievergelt, Caroline M, Mi, Shuangli, Brennand, Kristen J, Kelsoe, John R, Gage, Fred H, and Yao, Jun

Subjects
Stem Cell Research - Induced Pluripotent Stem Cell, Bipolar Disorder, Serious Mental Illness, Regenerative Medicine, Neurosciences, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Mental Health, Stem Cell Research, Brain Disorders, Mental health, Action Potentials, Antipsychotic Agents, Calcium Signaling, Dentate Gyrus, Endophenotypes, Humans, Induced Pluripotent Stem Cells, Lithium Compounds, Male, Mitochondria, Neurons, Patch-Clamp Techniques, Pharmacogenomics of Bipolar Disorder Study, General Science & Technology
Abstract

Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

Published
2015

33. Prevalence of Hypertension and Associated Risk Factors in Western Alaska Native People: The Western Alaska Tribal Collaborative for Health (WATCH) Study.

Author

Jolly, Stacey, Koller, Kathryn, Metzger, Jesse, Day, Gretchen, Silverman, Angela, Hopkins, Scarlett, Austin, Melissa, Boden-Albala, Bernadette, Ebbesson, Sven, Boyer, Bert, Howard, Barbara, and Umans, Jason

Subjects
Adult, Alaska, Blood Pressure Monitoring, Ambulatory, Cardiovascular Diseases, Cooperative Behavior, Female, Health Surveys, Humans, Hypertension, Inuit, Male, Middle Aged, Mortality, Prevalence, Risk Factors, Rural Population
Abstract

Hypertension is a common chronic disease and a key risk factor in the development of cardiovascular disease. The Western Alaska Tribal Collaborative for Health study consolidates baseline data from four major cohorts residing in the Norton Sound and Yukon-Kuskokwim regions of western Alaska. This consolidated cohort affords an opportunity for a systematic analysis of high blood pressure and its correlates in a unique population with high stroke rates over a wide age range. While the prevalence of hypertension among western Alaska Native people (30%, age-standardized) is slightly less than that of the US general population (33%), cardiovascular disease is a leading cause of mortality in this rural population. The authors found that improvement is needed in hypertension awareness as about two thirds (64%) of patients reported awareness and only 39% with hypertension were controlled on medication. Future analyses assessing risk and protective factors for incident hypertension in this population are indicated.

Published
2015

34. Cross-sectional survey comparing HIV risk behaviours of adolescent and young adult men who have sex with men only and men who have sex with men and women in the US and Puerto Rico

Author

Ellen, Jonathan M, Greenberg, Lauren, Willard, Nancy, Stines, Stephanie, Korelitz, James, and Boyer, Cherrie B

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Sciences, Prevention, Infectious Diseases, Behavioral and Social Science, HIV/AIDS, Drug Abuse (NIDA only), Substance Misuse, Prevention of disease and conditions, and promotion of well-being, Aetiology, 2.3 Psychological, social and economic factors, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Infection, Good Health and Well Being, Adolescent, Bisexuality, Cross-Sectional Studies, HIV Infections, Homosexuality, Male, Humans, Male, Prevalence, Puerto Rico, Risk Factors, Risk-Taking, Sexual Behavior, Sexual Partners, Substance-Related Disorders, United States, Unsafe Sex, Young Adult, Adolescent Medicine Trials Network for HIV/AIDS Interventions, ADOLESCENT, HETEROSEXUAL BEHAVIOUR, HIV, SEXUAL BEHAVIOUR, SEXUAL HEALTH, Medical Microbiology, Public Health and Health Services, Clinical sciences, Public health
Abstract

ObjectiveTo examine the HIV risk behaviours of men who have sex with men only (MSMO) and men who have sex with men and women (MSMW), aged 12-24 years, in five US cities and in San Juan, Puerto Rico.MethodsData were collected through four annual cross-sectional anonymous surveys at community venues and included questions about sexual partnerships, sexual practices including condom use and substance use. Demographic and risk profiles were summarised for both groups.ResultsA total of 1198 men were included in this analysis, including 565 MSMO and 633 MSMW. There were statistically significant differences between the two groups for many risk factors examined in multivariable models. MSMW were more likely to identify as bisexual, be in a long-term relationship, have a history of homelessness, have ever used marijuana, have ever been tested for HIV and to have been tested for HIV within the past 6 months. MSMW may be more likely to ever exchange sex for money and ever have a sexually transmitted infection than MSMO.ConclusionsMSMW were more likely to report several markers of socioeconomic vulnerability or behaviours associated with increased risk for HIV than MSMO. MSMW contribute to HIV prevalence in the USA, and better understanding of the risk profile of this group is essential to understand heterosexual HIV transmission. MSMW, particularly those who identify as bisexual or questioning, may feel uncomfortable participating in programmes that are designed for gay-identified men. Therefore, prevention strategies need to target distinct subgroups that compose the population of MSM.

Published
2015

35. A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP

Author

Morgan, Timothy R, Osann, Kathryn, Bottiglieri, Teodoro, Pimstone, Neville, Hoefs, John C, Hu, Ke-Qin, Hassanein, Tarek, Boyer, Thomas D, Kong, Lorene, Chen, Wen-Pin, Richmond, Ellen, Gonzalez, Rachel, Rodriguez, Luz M, and Meyskens, Frank L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis - C, Liver Disease, Prevention, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Chronic Liver Disease and Cirrhosis, Cancer, Liver Cancer, Digestive Diseases, Complementary and Integrative Health, Hepatitis, Hepatitis - B, Rare Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Oral and gastrointestinal, Good Health and Well Being, Antioxidants, Biomarkers, Double-Blind Method, Female, Hepatitis C, Humans, Liver Cirrhosis, Liver Function Tests, Male, Middle Aged, Oxidative Stress, Prospective Studies, Quality of Life, S-Adenosylmethionine, alpha-Fetoproteins, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential.

Published
2015

36. Co-Parenting Relationship Experiences of Black Adolescent Mothers in Active Romantic Partnerships With the Fathers of Their Children

Author

Nelson, LaRon E, Thach, Chia T, Shelton, Melissa M, and Boyer, Cherrie B

Subjects
Nursing, Health Sciences, Clinical Research, Pediatric, Behavioral and Social Science, Good Health and Well Being, Adolescent, Black or African American, Family Characteristics, Fathers, Female, Humans, Interviews as Topic, Male, Mothers, Parenting, adolescents, dyadic analysis, African American, co-parenting, interpretive description
Abstract

We conducted an interpretive description of co-parenting relationship experiences of romantically involved Black adolescent mothers and fathers with shared biological children. The study was conducted in Brooklyn, New York, using data from individual in-depth interviews with adolescent mothers and fathers (n = 10). Four themes were identified: (a) putting our heads together; (b) balancing childhood and parenthood; (c) less money, more problems; and (d) if we use condoms, it is for contraception. The co-parenting couples managed very complex relationships, but their mutual interest in the welfare of their children was a relational asset. Co-parents had sparse financial resources but used a moral economy strategy to provide mutual support. Future research is needed that focuses on identifying other co-parent relationship assets and integrating and evaluating their utility for enhancing interventions for adolescent families.

Published
2015

37. Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup’ik) population

Author

Vaughan, Laura Kelly, Wiener, Howard W, Aslibekyan, Stella, Allison, David B, Havel, Peter J, Stanhope, Kimber L, O’Brien, Diane M, Hopkins, Scarlett E, Lemas, Dominick J, Boyer, Bert B, and Tiwari, Hemant K

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Clinical Research, Human Genome, Obesity, American Indian or Alaska Native, Prevention, Genetics, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Stroke, Cancer, Cardiovascular, Oral and gastrointestinal, Metabolic and endocrine, Adult, Alaska, Anthropometry, Body Composition, Computational Biology, Cross-Sectional Studies, Diet, Fatty Acids, Omega-3, Female, Genetic Linkage, Genome, Human, Humans, Inuit, Male, Polymorphism, Single Nucleotide, Waist Circumference, Alaska Native, Linkage, n-3 fatty acids, Clinical Sciences, Endocrinology & Metabolism, Clinical sciences
Abstract

ObjectiveTo identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people.Material and methodsWe measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks.ResultsWe observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004).ConclusionsThis study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people.

Published
2015

38. Evaluation of the Effect of Human Immunodeficiency Virus–Related Structural Interventions: The Connect to Protect Project

Author

Ellen, Jonathan M, Greenberg, Lauren, Willard, Nancy, Korelitz, James, Kapogiannis, Bill G, Monte, Dina, Boyer, Cherrie B, Harper, Gary W, Henry-Reid, Lisa M, Friedman, Lawrence B, and Gonin, René

Subjects
Paediatrics, Biomedical and Clinical Sciences, Clinical Research, Infectious Diseases, Prevention, HIV/AIDS, Sexually Transmitted Infections, Behavioral and Social Science, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adolescent, Child, Condoms, Cross-Sectional Studies, Female, HIV Infections, Health Promotion, Health Surveys, Humans, Male, Risk Assessment, Risk Factors, Risk Reduction Behavior, Sexual Behavior, Sexually Transmitted Diseases, Viral, United States, Young Adult
Abstract

ImportanceWith the emphasis on structural-level interventions that target social determinants of human immunodeficiency virus (HIV) transmission to curb the HIV epidemic, there is a need to develop evaluation models that can detect changes in individual factors associated with HIV-related structural changes.ObjectiveTo describe whether structural changes developed and achieved by community coalitions are associated with an effect on individual factors associated with the risk of contracting HIV.Design, setting, and participantsIn this serial cross-sectional survey design, data were collected from 8 cities during 4 rounds of annual surveys from March 13, 2007, through July 29, 2010. Study recruitment took place at venues where the population of focus was known to congregate, such as clubs, bars, community centers, and low-income housing. The convenience sample of at-risk youth (persons aged 12-24 years) included 5337 individuals approached about the survey and 3142 (58.9%) who were screened for eligibility. Of the 2607 eligible participants, 2559 (98.2%) ultimately agreed to participate.InterventionsAchievement of locally identified structural changes that targeted public and private entities (eg, federal agencies, homeless shelters, and school systems) with the goal of fostering changes in policy and practice to ultimately facilitate positive behavioral changes aimed at preventing HIV.Main outcomes and measuresNumber of sexual partners, partner characteristics, condom use, and history of sexually transmitted infections and HIV testing.ResultsExposure to structural changes was not statistically significantly associated with any of the outcome measures, although some results were in the direction of a positive structural change effect (eg, a 10-unit increase in a structural change score had an odds ratio of 0.88 [95% CI, 0.76-1.03; P = .11] for having an older sexual partner and an odds ratio of 0.91 [95% CI, 0.60-1.39; P = .39] for using a condom half the time or less with a casual partner).Conclusions and relevanceThis study evaluated a broad representation of at-risk individuals and assessed the effect of numerous structural changes related to various HIV risk factors. No structural changes as measured in this study were associated with a statistically significant reduction in risk behaviors. These null findings underscore the need for a long-term approach in evaluating structural interventions and the development of more nuanced methods of quantifying and comparing structural-change initiatives and determining the appropriate strategies for evaluating effect.

Published
2015

39. Leadership in Adolescent Health: Developing the Next Generation of Maternal Child Health Leaders Through Mentorship

Author

Blood, Emily A, Trent, Maria, Gordon, Catherine M, Goncalves, Adrianne, Resnick, Michael, Fortenberry, J Dennis, Boyer, Cherrie B, Richardson, Laura, and Emans, S Jean

Subjects
Paediatrics, Biomedical and Clinical Sciences, Health Sciences, Pediatric, Good Health and Well Being, Adolescent, Adolescent Health Services, Adult, Cross-Sectional Studies, Education, Public Health Professional, Female, Health Personnel, Health Status, Humans, Interdisciplinary Studies, Leadership, Longitudinal Studies, Male, Maternal-Child Health Centers, Mentors, Professional Competence, Program Development, Program Evaluation, Quality Assurance, Health Care, Surveys and Questionnaires, United States, Mentorship, Developmental networks, Adolescent health, Medical and Health Sciences, Studies in Human Society, Public Health, Biomedical and clinical sciences, Health sciences, Human society
Abstract

Leadership development is a core value of Maternal Child Health Bureau training programs. Mentorship, an MCH Leadership Competency, has been shown to positively affect career advancement and research productivity. Improving mentorship opportunities for junior faculty and trainees may increase pursuit of careers in areas such as adolescent health research and facilitate the development of new leaders in the field. Using a framework of Developmental Networks, a group of MCH Leadership Education in Adolescent Health training program faculty developed a pilot mentoring program offered at the Society for Adolescent Health and Medicine Annual Meeting (2011-2013). The program matched ten interdisciplinary adolescent health fellows and junior faculty with senior mentors at other institutions with expertise in the mentee's content area of study in 2011. Participants were surveyed over 2 years. Respondents indicated they were "very satisfied" with their mentor match, and all agreed or strongly agreed that the mentoring process in the session was helpful, and that the mentoring relationships resulted in several ongoing collaborations and expanded their Developmental Networks. These results demonstrate that MCH programs can apply innovative strategies to disseminate the MCH Leadership Competencies to groups beyond MCH-funded training programs through programs at scientific meetings. Such innovations may enhance the structure of mentoring, further the development of new leaders in the field, and expand developmental networks to provide support for MCH professionals transitioning to leadership roles.

Published
2015

40. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Author

Bush, Sean P, Ruha, Anne-Michelle, Seifert, Steven A, Morgan, David L, Lewis, Brandon J, Arnold, Thomas C, Clark, Richard F, Meggs, William J, Toschlog, Eric A, Borron, Stephen W, Figge, Gary R, Sollee, Dawn R, Shirazi, Farshad M, Wolk, Robert, de Chazal, Ives, Quan, Dan, García-Ubbelohde, Walter, Alagón, Alejandro, Gerkin, Richard D, and Boyer, Leslie V

Subjects
Clinical Research, Hematology, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antivenins, Blood Coagulation Disorders, Child, Child, Preschool, Crotalid Venoms, Double-Blind Method, Female, Humans, Immunoglobulin Fab Fragments, Male, Middle Aged, Platelet Count, Prospective Studies, Snake Bites, Treatment Outcome, Viperidae, Young Adult, Snakes, Toxinology, Pharmacology and Pharmaceutical Sciences, Toxicology
Abstract

BackgroundCrotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation.MethodsWe conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8.Results121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness.ConclusionsIn this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Published
2015

41. A Comparison of Network-Based Strategies for Screening At-Risk Hispanic/Latino Adolescents and Young Adults for Undiagnosed Asymptomatic HIV Infection

Author

Boyer, Cherrie B, Robles-Schrader, Grisel M, Li, Su X, Miller, Robin L, Korelitz, James, Price, Georgine N, Torres, Carmen M Rivera, Chutuape, Kate S, Stines, Stephanie J, Straub, Diane M, Peralta, Ligia, Febo, Irma, Hightow-Weidman, Lisa, Gonin, René, Kapogiannis, Bill G, and Ellen, Jonathan M

Subjects
Public Health, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Pediatric, Prevention, Infectious Diseases, Clinical Research, HIV/AIDS, Pediatric AIDS, Clinical Trials and Supportive Activities, Infection, Good Health and Well Being, Adolescent, Adult, Community Health Services, Cross-Sectional Studies, Female, HIV Infections, Hispanic or Latino, Humans, Interviews as Topic, Male, Mass Screening, Prevalence, Puerto Rico, Risk, Risk Factors, Risk-Taking, Sexual Behavior, United States, Young Adult, Hispanic/Latino adolescents and young adults, HIV testing/screening, Network-based HIV screening, Hispanic Americans, Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

PurposeHispanic/Latino adolescents and young adults are disproportionately impacted by the HIV/AIDS epidemic; yet little is known about the best strategies to increase HIV testing in this group. Network-based approaches are feasible and acceptable means for screening at-risk adults for HIV infection, but it is unknown whether these approaches are appropriate for at-risk young Hispanics/Latinos. Thus, we compared an alternative venue-based testing (AVT) strategy with a social and sexual network-based interviewing and HIV testing (SSNIT) strategy.MethodsAll participants were Hispanics/Latinos aged 13-24 years with self-reported HIV risk; they were recruited from 11 cities in the United States and Puerto Rico and completed an audio computer-assisted self-interview and underwent HIV screening.ResultsA total of 1,596 participants (94.5% of those approached) were enrolled: 784 (49.1%) through AVT and 812 (50.9%) through SSNIT. HIV infection was identified in three SSNIT (.37%) and four AVT (.51%) participants (p = .7213).ConclusionsDespite high levels of HIV risk, a low prevalence of HIV infection was identified with no differences by recruitment strategy. We found overwhelming support for the acceptability and feasibility of AVT and SSNIT for engaging and screening at-risk young Hispanics/Latinos. Further research is needed to better understand how to strategically implement such strategies to improve identification of undiagnosed HIV infection.

Published
2014

42. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

Author

Malik, Deepika, Tarek, Mohamed, del Carpio, Javier Caceres, Ramirez, Claudio, Boyer, David, Kenney, M Cristina, and Kuppermann, Baruch D

Subjects
Eye Disease and Disorders of Vision, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Apoptosis, Bevacizumab, Cadaver, Cell Survival, Cells, Cultured, Humans, Macular Degeneration, Male, Ranibizumab, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Reference Values, Retinal Pigment Epithelium, Vascular Endothelial Growth Factor A, Young Adult, Angiogenesis, Macula, Treatment Medical, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

PurposeTo compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture.MethodsHuman retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death.ResultsCell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p

Published
2014

43. A Stable Isotope Biomarker of Marine Food Intake Captures Associations between n–3 Fatty Acid Intake and Chronic Disease Risk in a Yup’ik Study Population, and Detects New Associations with Blood Pressure and Adiponectin 1,2

Author

O’Brien, Diane M, Kristal, Alan R, Nash, Sarah H, Hopkins, Scarlett E, Luick, Bret R, Stanhope, Kimber L, Havel, Peter J, and Boyer, Bert B

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Clinical Research, Obesity, Cardiovascular, Nutrition, Metabolic and endocrine, Oral and gastrointestinal, Adiponectin, Adolescent, Adult, Alaska, Biomarkers, Blood Pressure, Chronic Disease, Cross-Sectional Studies, Eating, Fatty Acids, Omega-3, Female, Humans, Hypertension, Incidence, Inuit, Male, Metabolic Diseases, Middle Aged, Nitrogen Isotopes, Risk Factors, Seafood, Young Adult, Animal Production, Food Sciences, Nutrition & Dietetics, Animal production, Food sciences, Nutrition and dietetics
Abstract

The nitrogen isotope ratio (δ(15)N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ(15)N derives from marine protein, and these dietary components may have different biologic effects. Whether δ(15)N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ(15)N, and then in a larger (n = 772) cross-sectional study population using δ(15)N only. In the smaller sample, associations of RBC EPA, DHA, and δ(15)N with obesity and chronic disease risk factors were similar in direction and significance: δ(15)N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted β-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ(15)N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ(15)N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ(15)N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ(15)N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people.

Published
2014

44. T2D SNPs among Yup'ik people

Author

Klimentidis, Yann C, Lemas, Dominick J, Wiener, Howard H, O'Brien, Diane M, Havel, Peter J, Stanhope, Kimber L, Hopkins, Scarlett E, Tiwari, Hemant K, and Boyer, Bert B

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Obesity, Genetics, Diabetes, Nutrition, Human Genome, Prevention, American Indian or Alaska Native, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Alaska, Blood Glucose, Body Mass Index, Cyclin-Dependent Kinase 5, Diabetes Mellitus, Type 2, Diet, Fasting, Fatty Acids, Omega-3, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Glycated Hemoglobin, Homeodomain Proteins, Humans, Insulin, Inuit, Linear Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Prevalence, Risk Factors, Transcription Factors, Young Adult, tRNA Methyltransferases, Alaska Native, glycemic traits, n-3 polyunsaturated fatty acids, type 2 diabetes single nucleotide polymorphisms, n-3, 2, 阿拉斯加原住民，血糖特征，n-3多不饱和脂肪酸，2型糖尿病单核苷酸多态性, Clinical Sciences, Public Health and Health Services, Clinical sciences
Abstract

BackgroundGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations.MethodsIn 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score (GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index (BMI), and n-3 PUFA intake.ResultsThe rs7754840 SNP in CDKAL1 is significantly associated with HbA1c (P = 0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose (FG) and HbA1c measure (P = 0.00046) and with homeostatic model assessment of β-cell function (HOMA-B; P = 0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEX SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake.ConclusionOur results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.

Published
2014

45. A stable isotope biomarker of marine food intake captures associations between n-3 fatty acid intake and chronic disease risk in a Yup'ik study population, and detects new associations with blood pressure and adiponectin.

Author

O'Brien, Diane M, Kristal, Alan R, Nash, Sarah H, Hopkins, Scarlett E, Luick, Bret R, Stanhope, Kimber L, Havel, Peter J, and Boyer, Bert B

Subjects
Humans, Hypertension, Metabolic Diseases, Obesity, Chronic Disease, Nitrogen Isotopes, Fatty Acids, Omega-3, Incidence, Risk Factors, Cross-Sectional Studies, Blood Pressure, Eating, Seafood, Adolescent, Adult, Middle Aged, Inuits, Alaska, Female, Male, Adiponectin, Young Adult, Biomarkers, Fatty Acids, Omega-3, Nutrition and Dietetics, Animal Production, Food Sciences, Nutrition & Dietetics
Abstract

The nitrogen isotope ratio (δ(15)N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ(15)N derives from marine protein, and these dietary components may have different biologic effects. Whether δ(15)N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ(15)N, and then in a larger (n = 772) cross-sectional study population using δ(15)N only. In the smaller sample, associations of RBC EPA, DHA, and δ(15)N with obesity and chronic disease risk factors were similar in direction and significance: δ(15)N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted β-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ(15)N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ(15)N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ(15)N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ(15)N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people.

Published
2014

46. CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik people.

Author

Klimentidis, Yann C, Lemas, Dominick J, Wiener, Howard H, O'Brien, Diane M, Havel, Peter J, Stanhope, Kimber L, Hopkins, Scarlett E, Tiwari, Hemant K, and Boyer, Bert B

Subjects
Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Insulin, tRNA Methyltransferases, Blood Glucose, Fatty Acids, Omega-3, Homeodomain Proteins, Transcription Factors, Body Mass Index, Diet, Fasting, Prevalence, Linear Models, Risk Factors, Gene Frequency, Genotype, Polymorphism, Single Nucleotide, Adult, Middle Aged, Inuits, Alaska, Female, Male, Cyclin-Dependent Kinase 5, Young Adult, Glycated Hemoglobin A, Alaska Native, glycemic traits, n-3 polyunsaturated fatty acids, type 2 diabetes single nucleotide polymorphisms, 阿拉斯加原住民，血糖特征，n-3多不饱和脂肪酸，2型糖尿病单核苷酸多态性, n-3, 2, Diabetes Mellitus, Type 2, Hemoglobin A, Glycosylated, Fatty Acids, Omega-3, Polymorphism, Single Nucleotide, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations.MethodsIn 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score (GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index (BMI), and n-3 PUFA intake.ResultsThe rs7754840 SNP in CDKAL1 is significantly associated with HbA1c (P = 0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose (FG) and HbA1c measure (P = 0.00046) and with homeostatic model assessment of β-cell function (HOMA-B; P = 0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEX SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake.ConclusionOur results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.

Published
2014

47. DNA Methylation Patterns Are Associated with n–3 Fatty Acid Intake in Yup’ik People 1–3

Author

Aslibekyan, Stella, Wiener, Howard W, Havel, Peter J, Stanhope, Kimber L, O’Brien, Diane M, Hopkins, Scarlett E, Absher, Devin M, Tiwari, Hemant K, and Boyer, Bert B

Subjects
Heart Disease, Prevention, Cardiovascular, Genetics, Human Genome, Nutrition, Metabolic and endocrine, Adolescent, Adult, Aged, Alaska, Aquatic Organisms, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, DNA Methylation, Diabetes Mellitus, Diet, High-Fat, Epigenesis, Genetic, Erythrocytes, Fatty Acids, Omega-3, Female, Humans, Inuit, Male, Nitrogen Isotopes, Risk Factors, Animal Production, Food Sciences, Nutrition and Dietetics, Nutrition & Dietetics
Abstract

A large body of evidence links a high dietary intake of n-3 (ω-3) polyunsaturated fatty acids (PUFAs) with improved cardiometabolic outcomes. Recent studies suggested that the biologic processes underlying the observed associations may involve epigenetic changes, specifically DNA methylation. To evaluate changes in methylation associated with n-3 PUFA intake, we conducted an epigenome-wide methylation association study of long-chain n-3 PUFA intake and tested associations between the diabetes- and cardiovascular disease-related traits. We assessed DNA methylation at ∼470,000 cytosine-phosphate-guanine (CpG) sites in a cross-sectional study of 185 Yup'ik Alaska Native individuals representing the top and bottom deciles of PUFA intake. Linear regression models were used to test for the associations of interest, adjusting for age, sex, and community group. We identified 27 differentially methylated CpG sites at biologically relevant regions that reached epigenome-wide significance (P < 1 × 10⁻⁷). Specifically, regions on chromosomes 3 (helicase-like transcription factor), 10 (actin α 2 smooth muscle/Fas cell surface death receptor), and 16 (protease serine 36/C16 open reading frame 67) each harbored 2 significant correlates of n-3 PUFA intake. In conclusion, we present promising evidence of association between several biologically relevant epigenetic markers and long-term intake of marine-derived n-3 PUFAs.

Published
2014

48. Isotopic estimates of sugar intake are related to chronic disease risk factors but not obesity in an Alaska native (Yup’ik) study population

Author

Nash, SH, Kristal, AR, Bersamin, A, Choy, K, Hopkins, SE, Stanhope, KL, Havel, PJ, Boyer, BB, and O'Brien, DM

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Obesity, Nutrition, Arctic, Prevention, Cardiovascular, American Indian or Alaska Native, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, Adiponectin, Adult, Aged, Aged, 80 and over, Alaska, Biomarkers, Blood Pressure, Body Mass Index, Carbon Isotopes, Chronic Disease, Cross-Sectional Studies, Dietary Carbohydrates, Female, Humans, Indians, North American, Leptin, Linear Models, Male, Middle Aged, Nitrogen Isotopes, Risk Factors, Triglycerides, Waist Circumference, Young Adult, carbon, nitrogen, stable isotope ratio, chronic disease, risk factors, caloric sweeteners, Food Sciences, Human Movement and Sports Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

Background/objectivesSugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup'ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model. This study tested associations of isotopic estimates of sugar intake with body mass index (BMI), waist circumference (WC) and a broad array of other physiological and biochemical measures of chronic disease risk in Yup'ik people.Subjects/methodsIn a cross-sectional sample of 1076 Yup'ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors.ResultsIsotopic estimates of sugar intake were not associated with BMI (P=0.50) or WC (P=0.85). They were positively associated with blood pressure, triglycerides (TG) and leptin, and are inversely associated with total-, high-density lipoprotein- and low-density lipoprotein-cholesterol and adiponectin.ConclusionsIsotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup'ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup'ik people; however, longitudinal studies are required to understand associations with chronic disease incidence.

Published
2014

49. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY)

Author

Obbina Abani, Ali Abbas, Fatima Abbas, Joshua Abbas, Kasim Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Alison Abbott, Nabeel Abdallah, Ammar Abdelaziz, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Audrey Abdul, Basir Abdul, Siddiqui Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Abeer Ul Amna, Lynn Abel, Katrina Abernethy, Movin Abeywickrema, Chandra Abhinaya, Affyarsyah Abidin, Adebanke Aboaba, Abigail Aboagye-Odei, Christopher Aboah, Heba Aboelela, Hani Abo-Leyah, Karim Abouelela, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Ahmed Abousamra, Mona Abouzaid, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Rebecca Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yousuf Abusamra, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Faustina Acheampong, Prince Acheampong, Sarah Acheampong, Janet Acheson, Shiella Achieng, Andres Acosta, Rebecca Acquah, Catherine Acton, Jacqueline Adabie-Ankrah, Paul Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Marta Adamczyk, Carol Adams, Charlotte Adams, Daniel Adams, Kate Adams, Laura Adams, Nikkita Adams, Richard Adams, Tim Adams, Laura Adamu-Ikeme, Krishma Adatia, Kirsty Adcock, Lawrence Addai-Boampong, Afua Addo, Oluwatobi Adeagbo, Ade Adebiyi, Ogunlana Adedeji, Yewande Adegeye, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Femi W Adeoye, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Adedamola Adeyanju, Joyce Adeyemi, Tenifayo Adeyemo, Binay Adhikari, Shanti A Adhikari, Rina Adhikary, Adhikarla Aditya, Patience Adjepong, Gabrielle Adkins, Adnan Adnan, Marguerite Adriaanse, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Patricia Afrim, Felicia Akua Afriyie, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Laura Aguilar Jimenez, Jacqueline Afrakomah Agyekum, Kwame Agyen, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Afshan Ahmed, Ashar Ahmed, Asim Ahmed, Basheer A R Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Hanad Ahmed, Irshad Ahmed, Khaled Ahmed, Khalil Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rawya Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sana G Ahmed, Syed Ahmed, Syed H Ahmed, Roa Ahmed Ali, Bilal Ahmed Mohamud, Sana Ahmed, Sana Ahmer, Augustine Ahonia, Christine Aiken, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Bolutito Akinbiyi, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Mohammad Akram, Olugbenro Aktinade, Uzayr Akudi, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Adegoke Alabi, Narendra Aladangady, Mohamed Alafifi, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Albertus Albertus, Lorraine Albon, Angela Alcala, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Abdullah Aldesouki, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ram Maya Ale, Ana Alegria, Alison Alexander, Courtney Alexander, John Alexander, Peter D G Alexander, Julyan Al-fori, Laith Alghazawi, Osama Alhabsha, Bahij Al-Hakim, Rafil Alhameed, Mohammed Al-Hayali, Shams Al-Hity, Ali Ali, Amanda Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohamed Ali, Mohammad Ali, Muhammad S Ali, Nayab Ali, Oudai Ali, Ramla Ali, Sakina Ali, Syed Ali, Emilio Aliberti, Jade Alin, Abid Alina, Analyn Alipustain, Bachti Alisjahbana, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Abdullah Alkhudhayri, Moutaz Alkhusheh, Fiona Allan, Nataliya Allan, Alison Allanson, Robert Allcock, Eireann Allen, Jade Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Tania Allen, Abiola Alli, Kathryn Allison, Bethan Allman, Helen K Allsop, Lynne Allsop, David Allsup, Amal F T Almahroos, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Riyam Al-Sammarraie, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Fadia Alsheikh, Bashar Al-Sheklly, Sara Altaf, Amanda Alty, Mary Alvarez, Maria Alvarez Corral, Edward Alveyn, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Amel Amelia Ganefianty, Katharine Ames, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Badshah Amit, Amjad Amjad, Neelma Amjad, James Amoah-Dankwa, Victoria Amosun, Muhammad Amsal, Khaled Amsha, John Amuasi, Noelia Amutio Martin, Pugh Amy, Ann Anada, Atul Anand, Samantha Anandappa, Satya D Anantapatnaikuni, Ellen Anderson, Julie Anderson, Laura Anderson, Marina Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rebecca Anderson, Rory Anderson, Samantha Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Joyann Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Maldwyn Ansah, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Elena Apetri, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia F Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Samuel Archer, Simon Archer, Daniele Arcoria, Christian Ardley, Ana-Maria Arias, Oluwatoyin Aribike, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Jennifer Armistead, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Wendy Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Andrew Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Armena Arumaithurai, Ayush Arya, Rita Arya, Diptesh Aryal, Denisa Asandei, Adeeba Asghar, Malik Asghar, Arif Ashab, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Zakariya Ashfak, Ayesha Ashfaq, Abdul Ashish, Dawn Ashley, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Fiona J Ashworth, Rebecca Ashworth, Arshia Aslam, I Aslam, Suhail Aslam, Laura Aslett, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Abolaji Atomode, Brygitta Atraskiewicz, Abdul A Attia, Eva Attubato, Marie Attwood, Paula Aubrey, Zoltan Auer, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Hnin Wint Wint Aung, Ko Ko Aung, Kyaw Thu Aung, Nwe Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Malcolm Avari, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Abuzar Awadelkareem, Gabriel Awadzi, Mahmoud Awaly, Atia Awan, Aszad Aya, Eman Ayaz, John Maximilian Ayerh, Amanda Ayers, Jawwad Azam, Ahmed Azeem, Mohammed Azharuddin, Ammar Aziz, Ghazala Aziz, Imran Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Michel-Elie Bachour, Alisjahbana Bachti, Gina Bacon, Jenny Bacon, Bibi Badal, Aysha Badat, Maryuma Bader, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, Angela Bailey, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Lucy Bailey, Maria A Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Eilidh Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Danielle C Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Mark Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Ameet Bakhai, Nauman Bakhtiar, Panos Bakoulas, Dhanalakshmi Bakthavatsalam, Niranjan Balachandran, Andrea Balan, Prasath Balasingam, Theodosios Balaskas, Madhu Balasubramaniam, Nicola Balatoni, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Fiona Baldwin, Rebekah Baldwin-Jones, Nichola Bale, James Balfour, Matthew Ball, Robert Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Abeir Baltmr, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Santosh Baniya, Omar Bani-Saad, Harrison Banks, Luke Banks, Paul Banks, Claudia Bann, Helen Bannister, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Sharad Chandra Baral, Desislava Baramova, Russel Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Amanda Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Erandi Barker, Helen Barker, Joseph Barker, Leon Barker, Lesley Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Rory Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, Prince Gyenti Barning, William Barnsley, Andrew Barr, David Barr, James Barr, Charlotte Barr, Nina Barratt, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Sue Barrett, Esther Barrow, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, James Bartlett, Louise Bartlett, Shauna Bartley, Sandra Bartolmeu-Pires, Anna Barton, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Hannah Bashir, Archana Bashyal, Betsy Basker, Sudha Basnet, Buddha Basnyat, Ayten Basoglu, Alexander Basran, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Precious Basvi, Jireh A Batac, Vipula R Bataduwaarachchi, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Alice Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Tanveer Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Lee-Ann Bayo, 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Tak-Yan Ellis, Yvette Ellis, Alison C Ellwood, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed El-Naggar, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Mohammed A S A Elsayed, Sally El-Sayeh, Hana El-Sbahi, Mohammad Elsebaei, Tarek Elsefi, Karim El-Shakankery, Alguili Elsheikh, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Anna Emery, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Dickson Enenche, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Peter Eskander, Hanif Esmail, Fatheha Essa, Brynach Evans, Chris Evans, Debra Evans, E Evans, Emrys Evans, Gail Evans, Gareth Evans, Isabel Evans, Jack Evans, Jacqueline Evans, Jennifer Evans, John Evans, Jolanta Evans, Lisa Evans, Lynn Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Sharon Evans, Sian Evans, Teriann Evans, Tomos Evans, Caroline Everden, Serenydd Everden, Lynette Every, Hayley Evison, Lynsey Evison, Chiamaka Ezenduka, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Ian Fairbairn, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Ayaan Farah, Muna Farah, Qayyum Farah, Nowin Z Fard, Leila Fares, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Holly Farr, Aaron Farrell, Barbara Farrell, Fayed Farrukh, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Suman Fathima, Nibah Fatimah, Maria Faulkner, Saul N Faust, Clair Favager, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Aisthath Fazleen, Simon Fearby, Connie Fearnley, Alex Feben, Federico Fedel, Daria Fedorova, Christopher Fegan, Mae Felongo, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Ruth Fennelly, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Gloria Ferenando, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Jaime Fernandez Roman, Callum J Fernando, Jessica Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Sheldon Ferron, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Santos Filipa, Sarah A Filson, Shona Finan, Sarah Finbow, Deborah J Finch, Joanne Finch, Laurie Finch, Simon Finch, Spencer Finch, Natalie Fineman, Jim Finlayson, Lauren Finlayson, Adam Finn, Joanne Finn, Dylan Finnerty, Clare Finney, Deborah Finucane, Sofia Fiouni, Jo Fiquet, Promise Firi, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Carolyn Fitton, Felicity Fitzgerald, Fiona Fitzgerald, Karen Fitzjohn, Jan Flaherty, Michael Flanagan, Charles Flanders, Nikolaos Flaris, Gail Fleming, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Anna Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Fiona Flett, Karen Flewitt, Sarah Flockhart, Christopher Flood, Ian Floodgate, Jonathan Flor, Vincent Florence, Mary Flowerdew, Sharon Floyd, Margaret J Flynn, Rachel Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Paul Foley, Linda Folkes, Tracey Fong, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Helen R Foot, Jayne Foot, Jane Forbes, Amber Ford, Jamie Ford, Imogen Fordham, Jennifer Foreman, Matthew Forester, Mohammad Forkan, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Abigail Forsyth, Julian Forton, Conrad Foster, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Natasha Fowkes, Emily Fowler, Robert Fowler, Stephen Fowler, Amy Fox, Claire Fox, Heather Fox, Jonathan Fox, Laura Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Eva Fraile, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Siobhan Franklin, Catherine Fraser, Andi Fratila, Sharon Frayling, Martyn Fredlund, Anna Freeman, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Thomas French, Karen Freshwater, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Andrzej Frygier, Bridget Fuller, Liz Fuller, Lucy Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Zoë Gabriel, Hadiza Gachi, Sophie Gaffarena, Sarah Gage, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Babita Gajmer, Zacharoula Galani, Christopher Gale, Hugo Gale, Linda Gale, Rebecca Gale, Swetha Gali, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Feroze Gallam, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Anna Galvin, Victoria Galvis, Gareth Gamble, Laura Gamble, Liz Gamble, Brian Gammon, Chien N Gan, Muhammad B Ganaie, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Thenugan Ganeshanathan, Saibal Ganguly, Abrar Gani, Pauline Ganley, Ukraina Garcia, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Louis Gardner, Mark Garfield, Atul Garg, Isha Garg, Nathan Garlick, Daniel Garner, Justin Garner, Lucie Garner, Zoe Garner, Rosaline Garr, Kathryn A Garrero, Manisha Gartaula, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Sophie Gayle, Catherine Geddie, Ian Gedge, Sarah Gee, Fartuun Geele, Kalaichelvi Geerthan, Minnie Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Neal Gent, Susan Gent, Natalie Geoghegan, Aparna George, Bini George, Sam George, Susan George, Tina George, Valerie P George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Siobhan Gettings, Hisham Ghanayem, Bijan Ghavami Kia, Shaista Ghazal, Anca Gherman, Alison Ghosh, Dipansu Ghosh, Justin Ghosh, Subhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Chris Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Jamie Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Mary Gigi, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, James Gilham, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Lesley Gilmour, Louis Ginn, Franciscus Ginting, Theodora Giokanini-Royal, Anna Gipson, Barbie Giri, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Eleanor Glenday, Ana Glennon, Jodie Glossop, John Glover, Kyle Glover, Michelle Glover, Jan Glover Bengtsson, Deborah Glowski, Sharon Glynn, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Sarah Godlee, Emma Godson, Gillian Godwin, Sukanya Gogoi, Aiky Goh, Manjinder Gohel, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Vicky Goodall, Bob Goodenough, Anna Goodfellow, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Chris Gordon, Sally Gordon, Robin 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Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Jack Grenville, Jo Gresty, Susan Grevatt, Glaxy Grey, Samuel Gribben, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sandra Griffiths, Sarah Griffiths, Scott Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Evelina Grobovaite, Dorothy Grogono, Clarissa Grondin, Rachel Groome, Pauline Grose, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Jacinta Guerin, Sharazeq 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Hale, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alaina Halim, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Laura Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Jackie Halliday, Akmal Hallman, Heather Halls, Maryam Hamdollah-Zadeh, Ifedadepo A Hamed-Adekale, Bilal Hameed, Mohammed Hameed, Raph L Hamers, Imran Hamid, Mohamad Hamie, Raymond Hamill, Bethany Hamilton, Fergus Hamilton, Gus Hamilton, Leigh Hamilton, Melanie Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Emily Hammond, Leah Hammond, Sally Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, James A Hampson, Jude Hampson, Lucy Hampson, Lisa Hamzah, Jenny Han, Ozan Hanci, Sadiyah Hand, Lala Handayani, Jasmine Handford, Soran Handrean, Nina K Handzewniak, Sarah Haney, Vu Thi Kim Hang, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Helena Hanratty, Daniel Hansen, Anita Hanson, Ashley Hanson, Helen Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Ala Haqiqi, Monjurul Haque, Henry Harcourt, Lesley Harden, Zoe Harding, Simon Hardman, Marc Hardwick, Gareth Hardy, Joanna Hardy, Yasmine Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, James Hargraves, Carolyn Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Heather Harper, James Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Kate Harrington, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, Sophie Harris, David Harrison, Laura Harrison, Melanie Harrison, Olakunbi A Harrison, Rachael Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Jessica Hartley, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Alice Harvey, Angela Harvey, Anna Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Zoe Harzeli, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Jack Haslam, Zena Haslam, Grace Hasnip, Adil Hassan, Ali Hassan, Amro Hassan, Awab Hassan, Zeinab Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Sarah Hathaway-Lees, Jonathan Hatton, Jennifer Hau, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Lydia Hawker, Annie Hawkins, Joe Hawkins, Nancy Hawkins, W John Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Alasdair W Hay, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Carole Hays, Sarah Haysom, James Hayward, Patrick Haywood, Hazel Haywood Hasford, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Jessica L Healy, Amy Hearn, David Heasman, Angela Heath, Debbie Heath, Rowan Heath, Diane Heaton, Adam Heavens, Kerry Hebbron, Catherine Heckman, Gemma Hector, Sadie Heddon, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Richard Heinink, Rajdeep Heire, Ingvild Helgesen, Joanne Hemingway, Ulla Hemmila, Beth Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Eilidh Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Lucas E Hermans, Fe Marie Hernandez, Emma Heron, Lisa Heron, William Herrington, Emilia Heselden, Peta Heslop, Tracey Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Nicola Hewitson, Claire Hewitt, Davina Hewitt, Richard Hewitt, Samuel Hey, Robert S Heyderman, Mathis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, John Hickey, Naomi Hickey, Peter Hickey, Nicky Hickman, Alex Hicks, Jenny Hicks, Scott R Hicks, Phan Thi Thu Hien, Daniel Higbee, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Lisa Hill, Lucy Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Catherine Hillman-Cooper, Jon Hilton, Zoe Hilton, Sarah Hinch, Andrew Hindle, Esther Hindley, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Claire Hirst, Lindsay Hirst, Jemma Hives, Htet M Hlaing, Benson Ho, David K K Ho, Rosemary Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Christopher Hodge, Simon Hodge, Lesley Hodgen, George Hodgetts, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Mike Hodson, Alison Hogan, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Catherine Holbrook, Rebecca Holbrook, Catherine Holden, Jill Holden, Melinda Holden, Sophie Holden, Thomas Holder, Niels Holdhof, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Poppy Holland, Susan Holland, Marie L Hollands, Elizabeth Holliday, Kyra Holliday, Mark Holliday, Nina Holling, Laszlo Hollos, Nora Hollos, Leah Holloway, Simon Holloway, Max Hollowday, Marcus Hollyer, Amy Holman, Ann Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Beth Holroyd-Hind, Lyndsey Holt, Siobhan Holt, Susie Holt, Alexandra Holyome, Marie Home, Renate Homewood, Kate Hong, Louise Hoole, Clare Hooper, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Thomas Horne, Zoey Horne, Rebecca Horner, Caroline Horrobin, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Catherine Houghton, Kathryn Houghton, Rebecca Houlihan, Kay Housely, Hamish Houston, Roseanna Hovvels, Lee How, Laura Howaniec, Joanne Howard, Kate Howard, Laura Howard, Linda Howard, Lucy Howard, Megan Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Louise Howard-Sandy, Serena Howe, Alice Howell, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Ruth Howman, Josh Hrycaiczuk, Hein Htet, Naing Z Htoon, Su Htwe, Ying Hu, Chiang O H Huah, Sylvia Huang, Kelly Hubbard, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Suzanne Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Caitlin Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Martin Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Megan Hume, Charlotte Humphrey, Alasdair Humphries, Amy Humphries, Joanne Humphries, Charlotte Hunt, Fiona Hunt, Jane Hunt, Jonquil Hunt, Kristen Hunt, Luke Hunt, Molly Hunt, Sophie Hunt, Alexandra Hunter, Catherine Hunter, Ewan Hunter, Karl Hunter, Neil Hunter, Ross Hunter, Sophie Hunter, George Huntington, Fuad Huq, Elizabeth Hurditch, Judith Hurdman, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Afreen Hussain, Chreif Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Mohammed Hussain, Muhammad Hussain, Reda Hussain, Rizwana Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Samahir F E M Hussein, Ziad Hussein, Rebecca Hussey, Adiel Haqiq Hussien, Anja Hutchinson, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Nguyen Quang Huy, Thuong Huyen, Tran Bang Huyen, Nguyen Thi Huyen 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Jennings, Jacqui Jennings, Louise Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Greame Jervis, Ellen Jessup-Dunton, Jorge A Jesus Silva, Champa Jetha, Kishan Jethwa, Roshan Kumar Jha, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Simran Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Maya John, Navin John, Emma Johns, Margaret Johns, Antoinette Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Brogan Johnston, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Amy Jones, Angela Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Jac Jones, James Jones, Jonathon Jones, Julie Jones, Kate E Jones, Kimberly Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nancy Jones, Nicola Jones, Olivia Jones, Paul Jones, Philip H Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Susan Jones, Taya Jones, Thomas Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Michele Jordan, Sarah Jordan, Abi Jose, Litty Jose, Louise Jose, Sanal Jose, Anna Joseph, Gigee Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Tushar Joshi, Benz Josiah, Lijo Joy, Tiffany Joyce, Hong Ju, Adriel Ju Wen Kwek, Andrew Judd, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Nikhil Kadam, Nicole Kader, Ajai Kailey, Matthew Kain, Gail Kakoullis, Azad Kala Bhushan, Richard J K Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Thomas Kalmus Eliasz, Seika Kalsoom, Elisa Kam, 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Nicholas A Scriven, Angela Scullion, Therese Scullion, Emily Seager, Cathy Seagrave, Rebecca Seaman, Eleanor Sear, Isabella Seaton, Annette Seatter, Anna Seckington, Joanna Sedano, Gabrielle Seddon, Gemma Sedgwick, Yee Yong See, Muhammad A Seelarbokus, Christopher Sefton, Matias Segovia, Fatima Seidu, Gillian Sekadde, Faye Selby, Georgina Selby, Claire Sellar, Rachael Sellars, Katharine Sellers, Joseph Selley, Victoria Sellick, Gobika Selvadurai, Brintha Selvarajah, Haresh Selvaskandan, Subothini S Selvendran, Jeyakumar Selwyn, Alison Semmens, Gary Semple, Michael Sen, Nandini Sen, Seema Sen, Aditya Sengupta, Niladri Sengupta, Susana Senra, HoJan Senya, Teona Serafimova, Elisa Sernicola, Dheeraj Sethi, Shivam Sethi, Niranjan Setty, Abigail Seward, Teswaree Sewdin, Terri-Ann Sewell, Jack Seymour, Katherine Seymour, Hussam Shabbir, Fiona Shackley, Tariq Shafi, Faiza Shafique, Aashni Shah, Ahmar Shah, Anand Shah, Bhavni Shah, Hussun-Ara Shah, Momin Shah, Neil Shah, Pallav Shah, Priyank Shah, Qasim Shah, Rupal Shah, Sarfaraz H Shah, Snehal Shah, Suraj Shah, Syed Shah, Wajid Shah, Saarma Shahad, Sousan Shahi, Sipan Shahnazari, Najam Shahzad, Muhammad Shahzeb, Aisha Shaibu, Zara Shaida, Amina Y Shaikh, Maliha Shaikh, Rajit Shail, Mariya Shaji, Muhammad Shakeel, Roshni Shakya, Korah Shalan, Nadia Shamim, Ummulbaneen Shamji, Anindya Shams, Kazi Shams, Rasha Shamsah, Thomas Shanahan, Hamed Sharaf, Asir Sharif, Ajay Sharma, Ash Sharma, Bhawna Sharma, Mona Sharma, Ojasvi Sharma, Poonam Sharma, Rajeev Sharma, Sagar Sharma, Sanjeev Sharma, Sarkhara Sharma, Seema D Sharma, Shriv Sharma, Sonal Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Kerry Sharp, Louise M Sharp, Paula Sharratt, Phoebe Sharratt, Katherine Sharrocks, Serene Shashaa, Alexandra Shaw, Christopher Shaw, Daisy Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathon Shaw, Lisa Shaw, Michele Shaw, Tomos G Shaw, Anna Shawcross, James Shawcross, Jill Shawe, Lou Shayler, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, Noorann Sheikh, Benjamin Shelley, Sarah Shelton, Anil Shenoy, Julie Shenton, Sarah Shephardson, Amy Shepherd, Kate Shepherd, Lorna Shepherd, Scott Shepherd, Gareth Sheppard, Rhian Sheppeard, Helen Sheridan, Ray Sheridan, Samuel Sherridan, Leanne Sherris, Susanna Sherwin, Shaad Shibly, Fathimath F Shiham, Cassandra Shilladay, Ben Shillitoe, Delane Shingadia, Chiaki Shioi, Anand Shirgaonkar, Kim Shirley, Helen Shirt, Adebusola Shonubi, Jane Shoote, Ruth Shorrocks, Rob Shortman, Rohan Shotton, Sarah Shotton, Charmaine Shovelton, Ervin Shpuza, Anil Shrestha, Apurba Shrestha, Nora Shrestha, Reema Shrestha, Suchita Shrestha, Karen Shuker, Jonathan Shurlock, Jack Shurmer, Erfanur R Shuvo, Gilbert Siame, Loria Siamia, Moses Siaw-Frimpong, Seshnag Siddavaram, Nasir Siddique, Shahla Siddique, Sohail Siddique, Elaine Siddle, Emma Sidebotham, Jo Sidebottom, Roy Sievers, Katie Siggens, Nyma Sikondari, Ilman Silanas, Sofia V Silva, Claudia Silva Moniz, Malcolm Sim, Theresa Simangan, Vimbai Simbi, Robert Sime, George Simmons, Oliver Simmons, Richard Simms, Laura Simon, Merritt Simon, Natalie Simon, Samantha Simpkins, Angela Simpson, Anna Simpson, Danny Simpson, Georgina Simpson, Joanne Simpson, Kerry Simpson, Maria Simpson, Phillip Simpson, Thomas Simpson, Kathryn Simpson, Simon Sinclair, Cindy Sing, Ankita Singh, Claire Singh, Davinder Singh, Jayaprakash Singh, Jyoti Singh, Lokeshwar Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Saurabh Singh, Shivani Singh, Sumi Singh, Parag Singhal, Bryan Singizi, Vicky Singler, Manas Sinha, Punam Sinha, Sharad Sinha, Utkarsh Sinha, Guy Sisson, Sarah Sithiravel, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darsh Sivakumran, Sivanthi Sivanadarajah, Pasupathy-Rajah Sivasothy, Asok Skaria, Nicole Skehan, Robert Skelly, Orlagh Skelton, Imogen Skene, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Heather Slade, Mark Slade, Lynda Slater, Nicola Slawson, Rachel Slingsby, Andrew Sloan, Brendan Sloan, Derek Sloan, Geraldine Sloane, Malgorzata Slowinska, Benjamin Small, Ellen Small, Samuel Small, Adam Smallridge, Dawn Smalls, Karen Denise Smallshaw, Andy Smallwood, Brittany Smart, Lynne Smart, Justyna Smeaton, Carien Smit, Aileen Smith, Alex Smith, Amanda Smith, Amy Smith, Andrew Smith, Catherine Smith, Chris Smith, Christopher Smith, Coral Smith, Debra Smith, Dominic Smith, Eleanor Smith, Harriet Smith, Hazel Smith, Helen Smith, Jacky Smith, Jessica Smith, Kate Smith, Kerry Smith, Lara Smith, Linda Smith, Lisa Smith, Loren Smith, Maria Smith, Mark Smith, Martha A Smith, Mel Smith, Nicholas Smith, Oliver Smith, Philippa Smith, Rachel Smith, Rebecca Smith, Rheanna Smith, Richard Smith, Sally Smith, Samantha Smith, Stacey Smith, Stephanie Smith, Susan Smith, Tracy Smith, Victoria Smith, Imogen Smith, John Smith, Sue Smolen, Sara Smuts, Naoise Smyth, Annette Snell, David Snell, Luke Snell, Alfred So, Beng So, Michelle Soan, Toluleyi Sobande, Sonia Sobowiec Kouman, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Herminder Sohal, Roy Soiza, Olajumoke Solademi, Babak Soleimani, Amanda Solesbury, Mohamed Soliman, Bernadette Solis, Reanne Solly, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Sven Sommerfield, Govind Soni, Raj Sonia, Temi Sonoiki, Shiu-Ching Soo, Pavandeep Soor, Germander Soothill, Jennifer Soren, Apina Sothinathan, Pragalathan Sothirajah, Jessica Sousa, Najwa Soussi, Donna Southam, David Southern, Iain Southern, Louise Southern, Sara M Southin, Jessica Southwell, Thomas Southworth, Sandra Sowden, Jason Sowter, Claudia Spalding, Enti Spata, Catherine Speare, Katie Spears, Mark Spears, Lynne Speirs, Susan Speirs, Michelle Spence, Niamh Spence, Branwell Spencer, Gisele Spencer, Rebecca Spencer, Sue Spencer, Tom Spencer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Sarah Spray, Janet Spriggs, Oliver Spring, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, Shiva Sreenivasan, K Sri Paranthamen, Rajesh Srikantaiah, Koottalai Srinivasan, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Rhodri Stacey, Sybil Stacpoole, Louise Stadon, William J Stagg, Jocasta Staines, Nikki Staines, Katie Stammers, Roxana Stanciu, Grazyna Stanczuk, Thomas Standley, Brittany Staniforth, Andrew Stanton, Lisa Stanton, Robyn Staples, Simon Stapley, Natalie Staplin, Adam Stark, Elizabeth Starkey, David S Starnes, Michelle Starr, Rachel Stead, Clare Stebbing, Conor Steele, Henry Steer, John Steer, Vergnano Stefania, Paula Stefanowska, Femke Steffensen, Caroline Stemp, Emma Stenson, Alison Stephens, David Stephensen, Elaine Stephenson, Monique Sterrenburg, Jennifer Stevens, Melanie Stevens, Will Stevens, Amy Stevenson, Andrew Stevenson, Lesley Stevenson, Sarah Stevenson, Matthew Steward, Christopher Stewart, Claire Stewart, Colin Stewart, Dobree A Stewart, Katelyn Stewart, Keely Stewart, Kristina Stewart, McKenna Stewart, Melissa Stewart, Rachel Stewart, Richard Stewart, Jo Stickley, Gemma Stiller, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Danielle Stocker, Lynne Stockham, Paul Stockton, Emma Stoddard, Kevin Stoffberg, Chelsea Stokes, Chris Stokes, Ben Stone, Roisin Stone, Sarah Stone, Emma-Jane Stoner, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Catherine Strait, Emma Stratton, Jane Stratton, Sam Straw, Dieter Streit, Emma Stride, Sally Stringer, Sophia Strong-Sheldrake, Siske Struik, Carmel Stuart, Anna Stubbs, Harrison Stubbs, Ann Sturdy, Sharon Sturney, Matt Stuttard, Cristina Suarez, Karuna Subba, Christian P Subbe, Keerth Subramaniam, Manjula Subramanian, Vaidyanathan Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Peter Sugden, Putri A Suherman, Rudresh Sukla, Anila Sukumaran, Ezoubi Suleiman, Ali Suliman, Fatimah Suliman, Sugrah Sultan, Uun Sumardi, Samyukta Sundar, Radha Sundaram, Reka Sundhar, Edmond Sung, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Nayanika Suresh, Shilpa Suresh, Michael Surtees, C Susan, Danielle Suter, Rohan Suthar, Helen Sutherland, Rachel Sutherland, Rebecca Sutherland, Sara-Beth Sutherland, Dovile Sutinyte, Deborah Sutton, Sam Sutton, Siobhan Sutton, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Rose Swain, Thomas Swaine, Christopher Swales, Carla Swanson-Low, Tirion Swart, Stephen Sweetman, Ealish Swift, Paul Swift, Pauline Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Omair Syed, Catriona Sykes, Daisy Sykes, Eliot Sykes, Luke Sylvester, Declan Symington, Dominic Symon, Andrew Syndercombe, Zoe Syrimi, Jen Syson, Gemma Szabo, Denise Szabó, Tamas Szakmany, Nina Szarazova, Megan Szekely, Adele Szekeres, Matthew Szeto, Kinga Szymiczek, Maria Tadros, Amr Tageldin, Lucy Tague, Hasan Tahir, Muhammad Tahir, Michael Tai, Jennifer Tait, Abigail Takyi, Peter Talbot, Alison Talbot -Smith, James Talbot-Ponsonby, Richard Tallent, Bradley Tallon, Adrian Tan, Bee Theng Tan, Hock Tan, Huey Tan, Jenny Tan, Jun Seng Tan, Keith Tan, WeiTeen Tan, Anand Tana, Alex Tanner, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Anita Tantri, Tm Tanzil-Al-Imran, Hayley Tarft, Priyal Taribagil, Obaid Tarin, Syed Tariq, David Tarpey, Esther Tarr, Lisa Tarrant, Antonia Tasiou, Alex Tate, Margaret L Tate, Matthew Tate, Paul Tate, Kate Tatham, Silvia S Tavares, Vera Tavoukjian, Shao An Isaac Tay, Alexander Taylor, Beverley Taylor, Charlie Taylor, Charlotte A Taylor, David Taylor, Elisabeth Taylor, Holly Taylor, Janet Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tracey Taylor, Vicky Taylor, Victoria Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Francesca Teasdale, Jessica Teasdale, Katherine Teasdale, Julie Tebbutt, Caroline Tee, Izla Teeluck, Borja Tejero Moya, Rajni Tejwani, Adam Telfer, Vibha Teli, Jennifer Tempany, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Radoslaw Tereszkowski-Kaminski, Lynne Terrett, Louise Terry, Tesha Islami Monika Tesha, Dariusz Tetla, Shirish Tewari, Daniel Tewkesbury, Joana Texeira, ChiaLing Tey, Miriam Thake, Clare Thakker, Manish Thakker, Jayna Thakrar, Bishal Jung Thakuri, Bhavneet Thamu, Nguyen Thi Thao, Amita Thapa, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Lambrini Theocharidou, Phyu Thet, Kapeendran Thevarajah, Mayooran Thevendra, Nang Thiri Phoo, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Andrew Thomas, Caradog Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Helen Thomas, James Thomas, Jordan L Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Kirsty Thomasson, Rhian Thomas-Turner, Catherine Thompson, Christopher Thompson, Clara Thompson, Emma Thompson, Fiona Thompson, Hilary Thompson, Jessica Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Luke Thompson, Michael Thompson, Orla Thompson, Rebecca Thompson, Roger Thompson, Yolanda Thompson, Nicola Thomson, Patrick Thorburn, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Alice Thornton, Danielle Thornton, Jim Thornton, Richard Thornton, Sara Thornton, Susan Thornton, Thomas Thornton, Tracey Thornton, Christopher Thorpe, Nigel Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Genevieve Thueux, Pinky Thu-Ta, Vicky Thwaiotes, C Louise Thwaites, Guy Thwaites, Simon Tiberi, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Christopher Till, Amanda Tiller, Heather Tiller, John Timerick, Elizabeth Timlick, Alan Timmins, Alison Timmis, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Stephanie Tingley, Nicola Tinker, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Ajay Tirumalai Adisesh, Helen Tivenan, Katarzyna Tluchowska, Helen T-Michael, Anne Todd, Jackie Todd, Shirley Todd, Stacy Todd, Olga Toffoletti, Mohamed Tohfa, Sue Tohill, Melanie Tolson, Ana L Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Jo Tomlinson, Kerry Tomlinson, James Tonkin, Ivan Tonna, Catherine Toohey, Kirsty Topham, Mathew Topping, Audrey Torokwa, Collette Torrance, Omar Touma, Laura Tous Sampol, Ruhaif Tousis, Melissa Tout, Peter Tovey, Gareth Towersey, Jill Townley, Richard Tozer, Dang Khoa Tran, Hien Tran, Huyen Bang Tran, Michelle Tran, Nguyen Bao Tran, Van Giang Tran, Van Kien Tran, Helen Tranter, Jenny Travers, Christopher Travill, Sarah Traynor, Leanne Trethowan, Estefania Treus Gude, Mary Trevelyan, Nicola A Trewick, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Alex Trimmings, Tom Trinick, Kate Trivedi, Sven Troedson, Emily Tropman, Amy Trotter, Spyridon Trous, Helen Trower, Madeleine Trowsdale Stannard, Nigel Trudgill, Robert Truell, Nick Truman, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Tan Tsawayo, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Merika Tsitsi, Simon Tso, Natasha Tucker, Sally Tucker, Stephanie Tucker, Daisy E Tudor, Aisha Tufail, Jess Tuff, Jemma Tuffney, Redmond Tully, Tulus Tulus Satriasih, Grace Tunesi, Killiam Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Georgina Turner, Kate Turner, Kelly Turner, Kim Turner, Lucy Turner, Lynne C Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Sarah Turner, Victoria Turner, Ian Turner-bone, Sharon Turney, Jon Turvey, Conor Tweed, David Tweed, Rebecca Twemlow, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Amanda Tyler, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Ioannis Tzinieris, A Wahid Uddin, Mohammad S Uddin, Ruhama Uddin, Ruzena Uddin, Jacinta Ugoji, Edith N Ukaegbu, Mazhar Ul Haq, Waqar Ul Hassan, Zia Ul-Haq, Salamat Ullah, Sana Ullah, Sanda Ullah, Ju Um, Athavan Umaipalan, Anil Umate, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Ben Ummat, Emma Underhill, Charlotte Underwood, Jonathan Underwood, Adam Unsworth, Veerpal Uppal, Veerpal S Uppal, Gerry Upson, Masood Ur Rasool, Alison Uriel, Sebastian Urruela, Hiromi Uru, Jess Usher, Miranda Usher, Rebecca Usher, Alexandra Usher-Rea, Andrew Ustianowski, Effua Usuf, Febriansyah Nur Utomo, Hiromi Uzu, Linda C Vaccari, Uddhav Vaghela, Abhay Vaidya, Denny Vail, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Pramodh Vallabhaneni, Nick Vallotton, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Sarah Van Blydenstein, Lucia van Bruggen, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne van Koutrik, Alexander Van Loggerenberg, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Piyush Vanmali, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Anna-Nektaria Varouxaki, Resti Varquez, Valeria Vasadi, Olivia Vass, Katherine Vassell, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Sue Vaughan, Heloyes Vayalaman, Darini Vayapooree, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Aravind Velugupati, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Michelle Venter, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Liberty Verueco, Jerik Verula, Anna Veterini, Natalie Vethanayagam, Shambavi Vettikumaran, Lucy Veys, Carinna Vickers, Saji Victor, SImpson Victoria, Celine P Vidaillac, Jennifer Vidler, Bavithra Vijayakumar, Vinod W Vijayaraghavan Nalini, Brigita Vilcinskaite, Alicija Vileito, Neringa Vilimiene, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Olivia Vincent, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Martina Vitaglione, Karunakaran Vithian, Sorice Vittoria, Sankkita Vivekananthan, Elena Vlad, Ben Vlies, Linda von Oven, Claire Vooght, Kim Thi Vu Thai, Kritchai Vutipongsatorn, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Phillip Wade, Jonathan Wadsley, Kirsten Wadsworth, Syed E I Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Alicia Waite, Rachel Wake, Alice Wakefield, William Wakeford, Fiona Wakinshaw, Emma Waldeck, Andrew Walden, Lorna Walding, Alexandria Waldron, Joanne Waldron, Emma Wales, Batool Wali, Danielle Walker, Gemma Walker, Harriet Walker, Ian Walker, Kevin Walker, Kim Walker, Lauren Walker, Linda Walker, Lynne Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Sara Walker, Susan Walker, Gillian Wallace, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Matthew Wallis, Emma Walmsley, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Maisie Walton, Michael Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Junita Wanda, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Shentong Wang, Deborah Warbrick, Samantha Warburton, Christopher Ward, Deborah Ward, Emma Ward, Hannah Ward, Janice Ward, Joanna Ward, Luke Ward, Nicola Ward, Rachael Ward, Thomas Ward, Tom Ward, Scott A Warden, Gibril Wardere, Steve Wardle, Hassan Wardy, Gareth Waring, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Rebecca Warren, Yolanda Warren, Davina Warrender, Hannah Warren-Miell, Adilia Warris, Gill Warwick, Helen Wassall, Sean Wasserman, Elizabeth Wasson, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Abigail Watkin, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Abigail Watson, Adam J R Watson, Ekaterina Watson, Eleanor Watson, Felicity Watson, J G R Watson, Louisa Watson, Paul Watson, Rebecca Watson, Robert Watson, Kathleen Watson, Malcolm Watters, Donna Watterson, Khairiah Wattimena, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Matthew Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Chloe Webb, Claire Webb, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Jemma Webster, Tim Webster, Jordan Wedlin, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Emma Welch, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Benjamin Welham, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Victoria Wenn, Lauren Wentworth, Joan Wesonga, Kate Wesseldine, Joe West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Kelly Westwood, Sharon Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Andrew White, Ayesha White, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Nikki White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Kelly Whitehorn, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Louiza Whiteley, Sophie Whiteley, Rachael Whitham, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Ashleigh Wignall, Christopher Wignall, Annamaria Wilce, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Ben Wild, Laura Wild, Stephen Wild, Michael Wilde, Laura Wilding, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Anna Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Eleri Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, Heledd Williams, James Williams, Jennie Williams, Jill Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Mandy Williams, Marie Williams, Mark Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachel Williams, Robin Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Steffan Williams, Tamanna Williams, Tania Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Jodie Williamson, Rachel Williamson, Helen Williamson, Elaine Willis, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Jayne Willson, Alison Wilson, Andrea Wilson, Anna Wilson, Antoinette Wilson, Billy Wilson, David Wilson, Imogen Wilson, James Wilson, Karen Wilson, Kate Wilson, Kristy-Ann Wilson, Lucinda Wilson, Mark Wilson, Stephen Wilson, Toni Wilson, John Wilson, Khin Lei Yee Win, Marlar Win, Than Win, Tin Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Stuart Winearl, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Joseph Winterton, Hannah Winwood, Jack Wischhusen, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Tabitha WIshlade, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Chi-Man Wong, Edwin Wong, Jessica S Y Wong, Kit Y Wong, Mei Yin Wong, Nick Wong, Sam Wong, Ting Wong, Aaron B Wongkyezeng, Amanda Wood, Caroline Wood, Dianne Wood, Fiona Wood, Gordon Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Madeleine Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Myles Woodman, Stephen Woodmansey, Charlotte Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Holly Wright, Imogen Wright, Lianne Wright, Rachel Wright, Sarah Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Subie Wurie, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Bingru E Xia, Zhongyang Xia, Effua Yacoba, Santosh Yadav, Masseh Yakubi, May Yan, Yuuki Yanagisawa, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Jessica Ye, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Lam Minh Yen, Alastair Yeoh, Chun Yu Yeung, Peter Yew, Durgesh Yewatkar, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Hartantri Yovita, Chrissie Yu, Jack S J Yuan, Nindya Yufaniaputri, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Mahrukh Zainab, Thornton Zak, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Marcelina Zawadzka, Mohammed Zayed, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Darius Zeinali, Jing Zhang, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eva Zincone, Garikai Zindoga, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Letizia Zitter, Arkadiusz Zmierczak, Garazi Zubikarai, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, and Group, RECOVERY Collaborative

Subjects
Adult, Male, Hypoxia/etiology, SARS-CoV-2, COVID-19, 3rd-DAS, General Medicine, Adrenal Cortex Hormones/therapeutic use, AC, Dexamethasone/therapeutic use, Hospitals, Oxygen, Treatment Outcome, SDG 3 - Good Health and Well-being, MCP, Humans, Female
Abstract

Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation Findings Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). Interpretation In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Funding UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

Published
2023

50. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

Author

Ulrich Gatzemeier, Michael Boyer, Paolo Paoletti, Salih Emri, Christian Manegold, Claude Denham, Nicholas J. Vogelzang, James J. Rusthoven, James T. Symanowski, Clet Niyikiza, E. Kaukel, and Pierre Ruffié

Subjects
Oncology, Adult, Male, Mesothelioma, medicine.medical_specialty, Cancer Research, Guanine, Maximum Tolerated Dose, medicine.drug_class, medicine.medical_treatment, Pleural Neoplasms, Pemetrexed, Antimetabolite, Risk Assessment, Drug Administration Schedule, Pleural disease, Glutamates, Reference Values, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Single-Blind Method, Survival analysis, Aged, Neoplasm Staging, Probability, Cisplatin, Aged, 80 and over, Chemotherapy, Dose-Response Relationship, Drug, business.industry, Hazard ratio, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Surgery, Treatment Outcome, Multivariate Analysis, Female, business, medicine.drug
Abstract

PURPOSE Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months ( P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm ( P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

Published
2023

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