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1. Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity.

Author

Matilainen, Johanna, Berg, Viivi, Vaittinen, Maija, Impola, Ulla, Mustonen, Anne-Mari, Männistö, Ville, Malinen, Marjo, Luukkonen, Veera, Rosso, Natalia, Turunen, Tanja, Käkelä, Pirjo, Palmisano, Silvia, Arasu, Uma, Sihvo, Sanna, Aaltonen, Niina, Härkönen, Kai, Caddeo, Andrea, Kaminska, Dorota, Pajukanta, Päivi, Kaikkonen, Minna, Tiribelli, Claudio, Käkelä, Reijo, Laitinen, Saara, Pihlajamäki, Jussi, Nieminen, Petteri, and Rilla, Kirsi

Subjects
Adipocyte, Adipose tissue, Extracellular vesicles, Fatty acids, Inflammation, Obesity, Humans, Extracellular Vesicles, Obesity, Adipocytes, Inflammation, Adipose Tissue, Lipid Metabolism, Female, Male, Adult, Fatty Acids
Abstract

BACKGROUND: Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesitys impact on EV secretion from human AT remains limited. METHODS: We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. RESULTS: EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. CONCLUSIONS: We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

Published
2024

2. Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

Author

Dewey, Kathryn G, Wessells, K Ryan, Arnold, Charles D, Prado, Elizabeth L, Abbeddou, Souheila, Adu-Afarwuah, Seth, Ali, Hasmot, Arnold, Benjamin F, Ashorn, Per, Ashorn, Ulla, Ashraf, Sania, Becquey, Elodie, Bendabenda, Jaden, Brown, Kenneth H, Christian, Parul, Colford, John M, Dulience, Sherlie JL, Fernald, Lia CH, Galasso, Emanuela, Hallamaa, Lotta, Hess, Sonja Y, Humphrey, Jean H, Huybregts, Lieven, Iannotti, Lora L, Jannat, Kaniz, Lartey, Anna, Le Port, Agnes, Leroy, Jef L, Luby, Stephen P, Maleta, Kenneth, Matias, Susana L, Mbuya, Mduduzi NN, Mridha, Malay K, Nkhoma, Minyanga, Null, Clair, Paul, Rina R, Okronipa, Harriet, Ouédraogo, Jean-Bosco, Pickering, Amy J, Prendergast, Andrew J, Ruel, Marie, Shaikh, Saijuddin, Weber, Ann M, Wolff, Patricia, Zongrone, Amanda, and Stewart, Christine P

Subjects
Humans, Child Nutrition Disorders, Lipids, Child Development, Nutritional Status, Dietary Supplements, Child, Preschool, Infant, Africa South of the Sahara, Haiti, Bangladesh, Female, Male, Randomized Controlled Trials as Topic, Infant Nutritional Physiological Phenomena, Effect Modifier, Epidemiologic, child undernutrition, complementary feeding, home fortification, nutrient supplements, stunting, wasting, Clinical Trials and Supportive Activities, Clinical Research, Nutrition, Pediatric, Prevention, Zero Hunger, Good Health and Well Being, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (

Published
2021

3. Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

Author

Prado, Elizabeth L, Arnold, Charles D, Wessells, K Ryan, Stewart, Christine P, Abbeddou, Souheila, Adu-Afarwuah, Seth, Arnold, Benjamin F, Ashorn, Ulla, Ashorn, Per, Becquey, Elodie, Brown, Kenneth H, Chandna, Jaya, Christian, Parul, Dentz, Holly N, Dulience, Sherlie JL, Fernald, Lia CH, Galasso, Emanuela, Hallamaa, Lotta, Hess, Sonja Y, Huybregts, Lieven, Iannotti, Lora L, Jimenez, Elizabeth Y, Kohl, Patricia, Lartey, Anna, Le Port, Agnes, Luby, Stephen P, Maleta, Kenneth, Matchado, Andrew, Matias, Susana L, Mridha, Malay K, Ntozini, Robert, Null, Clair, Ocansey, Maku E, Parvez, Sarker M, Phuka, John, Pickering, Amy J, Prendergast, Andrew J, Shamim, Abu A, Siddiqui, Zakia, Tofail, Fahmida, Weber, Ann M, Wu, Lee SF, and Dewey, Kathryn G

Subjects
Humans, Lipids, Child Development, Language Development, Motor Skills, Socioeconomic Factors, Dietary Supplements, Child, Preschool, Infant, Africa South of the Sahara, Haiti, Bangladesh, Female, Male, Randomized Controlled Trials as Topic, Infant Nutritional Physiological Phenomena, Effect Modifier, Epidemiologic, child undernutrition, complementary feeding, executive function, language development, motor development, nutrient supplements, social-emotional development, Pediatric, Clinical Research, Clinical Trials and Supportive Activities, Zero Hunger, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.ObjectivesWe aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).ResultsIn 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsChild SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Published
2021

4. Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

Author

Wessells, K Ryan, Arnold, Charles D, Stewart, Christine P, Prado, Elizabeth L, Abbeddou, Souheila, Adu-Afarwuah, Seth, Arnold, Benjamin F, Ashorn, Per, Ashorn, Ulla, Becquey, Elodie, Brown, Kenneth H, Byrd, Kendra A, Campbell, Rebecca K, Christian, Parul, Fernald, Lia CH, Fan, Yue-Mei, Galasso, Emanuela, Hess, Sonja Y, Huybregts, Lieven, Jorgensen, Josh M, Kiprotich, Marion, Kortekangas, Emma, Lartey, Anna, Le Port, Agnes, Leroy, Jef L, Lin, Audrie, Maleta, Kenneth, Matias, Susana L, Mbuya, Mduduzi NN, Mridha, Malay K, Mutasa, Kuda, Naser, Abu M, Paul, Rina R, Okronipa, Harriet, Ouédraogo, Jean-Bosco, Pickering, Amy J, Rahman, Mahbubur, Schulze, Kerry, Smith, Laura E, Weber, Ann M, Zongrone, Amanda, and Dewey, Kathryn G

Subjects
Humans, Anemia, Anemia, Iron-Deficiency, Lipids, Micronutrients, Nutritional Status, Dietary Supplements, Child, Preschool, Infant, Africa South of the Sahara, Bangladesh, Female, Male, Randomized Controlled Trials as Topic, Infant Nutritional Physiological Phenomena, Effect Modifier, Epidemiologic, anemia, child undernutrition, complementary feeding, home fortification, iron deficiency, micronutrient status, nutrient supplements, Pediatric, Clinical Research, Clinical Trials and Supportive Activities, Nutrition, Prevention, Hematology, 3.3 Nutrition and chemoprevention, Prevention of disease and conditions, and promotion of well-being, Zero Hunger, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers.ResultsSQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin 12 mo and provided 9 (as opposed to

Published
2021

5. Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study

Author

Macedo, Etienne, Hemmila, Ulla, Sharma, Sanjib Kumar, Claure-Del Granado, Rolando, Mzinganjira, Henry, Burdmann, Emmanuel A, Cerdá, Jorge, Feehally, John, Finkelstein, Fredric, García-García, Guillermo, Jha, Vivekanand, Lameire, Norbert H, Lee, Euyhyun, Levin, Nathan W, Lewington, Andrew, Lombardi, Raúl, Rocco, Michael V, Aronoff-Spencer, Eliah, Tonelli, Marcello, Yeates, Karen, Remuzzi, Giuseppe, and Mehta, Ravindra L

Subjects
Clinical Research, Kidney Disease, HIV/AIDS, Prevention, Renal and urogenital, Good Health and Well Being, Acute Kidney Injury, Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Bolivia, Child, Child, Preschool, Creatinine, Developing Countries, Disease Progression, Feasibility Studies, Female, Humans, Infant, Malawi, Male, Middle Aged, Nepal, Point-of-Care Testing, Urinalysis, ISN 0by25 Trial Study Group, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundAcute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.Methods and findingsPatients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.ConclusionsThis multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Published
2021

6. Metabolomics‐related nutrient patterns at seroconversion and risk of progression to type 1 diabetes

Author

Johnson, Randi K, Vanderlinden, Lauren A, DeFelice, Brian C, Uusitalo, Ulla, Seifert, Jennifer, Fan, Sili, Crume, Tessa, Fiehn, Oliver, Rewers, Marian, Kechris, Katerina, and Norris, Jill M

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Nutrition, Diabetes, Pediatric, Autoimmune Disease, Metabolic and endocrine, Autoimmunity, Child, Child, Preschool, Diabetes Mellitus, Type 1, Diet, Disease Progression, Female, Humans, Islets of Langerhans, Male, Metabolomics, Nutrients, Proportional Hazards Models, Risk Factors, Seroconversion, Surveys and Questionnaires, dietary intake, metabolomics, nutrient patterns, progression, T1D, Paediatrics and Reproductive Medicine, Endocrinology & Metabolism, Clinical sciences, Paediatrics
Abstract

ObjectiveOur aim was to elucidate the role of diet in type 1 diabetes (T1D) by examining combinations of nutrient intake in the progression from islet autoimmunity (IA) to T1D.MethodsWe measured 2457 metabolites and dietary intake at the time of seroconversion in 132 IA-positive children in the prospective Diabetes Autoimmunity Study in the Young. IA was defined as the first of two consecutive visits positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). By December 2018, 40 children progressed to T1D. Intakes of 38 nutrients were estimated from semiquantitative food frequency questionnaires. We tested the association of each metabolite with progression to T1D using multivariable Cox regression. Nutrient patterns that best explained variation in candidate metabolites were identified using reduced rank regression (RRR), and their association with progression to T1D was tested using Cox regression adjusting for age at seroconversion and high-risk HLA genotype.ResultsIn stepwise selection, 22 nutrients significantly predicted at least two of the 13 most significant metabolites associated with progression to T1D, and were included in RRR. A nutrient pattern corresponding to intake lower in linoleic acid, niacin, and riboflavin, and higher in total sugars, explained 18% of metabolite variability. Children scoring higher on this metabolite-related nutrient pattern at seroconversion had increased risk for progressing to T1D (HR = 3.17, 95%CI = 1.42-7.05).ConclusionsCombinations of nutrient intake reflecting candidate metabolites are associated with increased risk of T1D, and may help focus dietary prevention efforts.

Published
2020

7. Strategies and barriers to achieving the goal of Finland’s tobacco endgame

Author

Timberlake, David S, Laitinen, Ulla, Kinnunen, Jaana M, and Rimpela, Arja H

Subjects
Policy and Administration, Public Health, Health Sciences, Human Society, Tobacco Smoke and Health, Tobacco, Clinical Research, Prevention, Cancer, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Female, Finland, Health Policy, Health Promotion, Humans, Male, Middle Aged, Organizational Objectives, Smoking Cessation, Tobacco Use, media, end game, disparities, cessation, global health
Abstract

ObjectivesFinland boldly legislated the end of tobacco use in its 2010 Tobacco Act, and subsequently expanded the goal in 2016 to eradicate other nicotine-containing products. This study explored stakeholders' perceptions about the strengths, barriers, solutions and rationale for Finland's comprehensive but conventional strategy to achieve its nicotine-free goal.DesignStudy participants were selected based on expertise in policy or practice of tobacco control (n=32). Semi-structured interviews, conducted in 2017 and 2018, covered topics ranging from consensus among stakeholders to Finland's ranking on the 2016 Tobacco Control Scale. The framework method was chosen for analysing interview transcripts.ResultsA perceived strength of Tobacco-Free Finland 2030 was the consensus and cooperation among members of the tobacco control community. The objective of becoming a nicotine- versus smoke-free society had almost unanimous support, challenged by a small minority who argued for greater discussion of harm reduction approaches. The need for maintaining legitimacy and historical successes in tobacco control were reasons for using a conventional strategy. Barriers to achieving the endgame goal included insufficient funding and over-reliance on non-governmental organisations, political/legal constraints, impact of institutional practices on tobacco disparities, ambivalence about the role of mass media and lack of prioritising smoking cessation.ConclusionsStakeholders' broad confidence in reaching the goal of Finland's tobacco endgame suggests that future policy initiatives will reflect the current, conventional strategy. If the Finnish government chooses to continue this approach, then it should designate separate funds for Tobacco-Free Finland 2030 and implement structural changes that will facilitate tobacco control initiatives.

Published
2020

8. Environmental exposures and child and maternal gut microbiota in rural Malawi

Author

Kortekangas, Emma, Kamng'ona, Arox W, Fan, Yue‐Mei, Cheung, Yin Bun, Ashorn, Ulla, Matchado, Andrew, Poelman, Basho, Maleta, Kenneth, Dewey, Kathryn G, and Ashorn, Per

Subjects
Public Health, Health Sciences, Clinical Research, Pediatric, Nutrition, Aetiology, 2.2 Factors relating to the physical environment, Zero Hunger, Adult, Bacteria, Child Nutrition Disorders, Child, Preschool, Educational Status, Environmental Exposure, Feces, Female, Gastrointestinal Microbiome, HIV Infections, Humans, Infant, Infant Nutrition Disorders, Malawi, Male, Nutrition Assessment, Nutritional Support, Socioeconomic Factors, child health, environment, gut microbiota, seasons, socio-economic factors, Paediatrics and Reproductive Medicine, Public Health and Health Services, Epidemiology, Paediatrics, Reproductive medicine
Abstract

BackgroundGut microbiota composition is associated with child health, but the effect of the environment on microbiota composition is not well understood. Few studies have been conducted in low-income settings where childhood malnutrition is common and possibly related to microbiota composition.ObjectivesTo investigate whether gut microbiota composition in young children and their mothers is associated with different environmental exposures in rural Malawi. We hypothesized that more adverse environmental exposures would be associated with lower levels of microbiota maturity and diversity.MethodsFaecal samples from up to 631 children and mothers participating in a nutrition intervention trial were collected at 1, 6, 12, 18, and 30 months (children) and at 1 month (mothers) after birth and analysed for microbiota composition with 16S rRNA sequencing. Bacterial OTU and genus abundances, measures of microbiota maturity and diversity, and UniFrac distances were compared between participants with different environmental exposures. The exposure variables included socio-economic status, water source, sanitary facility, domestic animals, maternal characteristics, season, antibiotic use, and delivery mode.ResultsMeasures of microbiota maturity and diversity in children were inversely associated with maternal education at 6, 18, and 30 months and did not otherwise differ consistently between participants with different environmental exposures. Phylogenetic distance was related to season of stool sample collection at all time points. At the level of individual OTUs and genera, season of stool sample collection, type of water source, and maternal education showed most associations with child gut microbiota, while HIV status was the most important predictor of relative OTU and genus abundances in mothers.ConclusionThe results do not support the hypothesis that adverse environmental exposures are broadly associated with lower microbiota maturity and diversity but suggest that environmental exposures influence the abundance of several bacterial OTUs and genera and that low maternal education is associated with higher microbiota maturity and diversity.

Published
2020

9. Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi

Author

Hughes, Riley L, Arnold, Charles D, Young, Rebecca R, Ashorn, Per, Maleta, Ken, Fan, Yue-Mei, Ashorn, Ulla, Chaima, David, Malamba-Banda, Chikondi, Kable, Mary E, and Dewey, Kathryn G

Subjects
Microbiology, Biological Sciences, Pediatric, Nutrition, Clinical Trials and Supportive Activities, Complementary and Integrative Health, Clinical Research, Oral and gastrointestinal, Cohort Studies, Dietary Supplements, Feces, Female, Gastrointestinal Microbiome, Humans, Infant, Infant Nutritional Physiological Phenomena, Inflammation, Lipids, Malawi, Male, Maternal Nutritional Physiological Phenomena, Micronutrients, Mothers, Nutritional Status
Abstract

An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.

Published
2020

10. The association of gut microbiota characteristics in Malawian infants with growth and inflammation.

Author

Kamng'ona, Arox W, Young, Rebecca, Arnold, Charles D, Kortekangas, Emma, Patson, Noel, Jorgensen, Josh M, Prado, Elizabeth L, Chaima, David, Malamba, Chikondi, Ashorn, Ulla, Fan, Yue-Mei, Cheung, Yin B, Ashorn, Per, Maleta, Kenneth, and Dewey, Kathryn G

Subjects
Humans, Inflammation, Body Weight, Body Size, Growth and Development, Adult, Infant, Malawi, Female, Male, Gastrointestinal Microbiome
Abstract

We tested the hypotheses that a more mature or diverse gut microbiota will be positively associated with infant growth and inversely associated with inflammation. We characterized gut microbiota from the stool samples of Malawian infants at 6 mo (n = 527), 12 mo (n = 632) and 18 mo (n = 629) of age. Microbiota diversity and maturity measurements were based on Shannon diversity index and microbiota for age Z-score (MAZ), respectively. Growth was calculated as change in Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HCZ) from 6 to 12 mo and 12 to 18 mo. Biomarkers of inflammation (alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) were measured at 6 and 18 mo. Multivariable models were used to assess the association of each independent variable with each outcome. Microbiota diversity and maturity were related to growth in weight from 6 to 12 mo, but not to growth in length or head circumference or to growth from 12 to 18 mo. Microbiota diversity and maturity may also be linked to inflammation, but findings were inconsistent.

Published
2019

11. Maternal and Infant Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Increases Infants’ Iron Status at 18 Months of Age in a Semiurban Setting in Ghana: A Secondary Outcome Analysis of the iLiNS-DYAD Randomized Controlled Trial

Author

Adu-Afarwuah, Seth, Young, Rebecca T, Lartey, Anna, Okronipa, Harriet, Ashorn, Per, Ashorn, Ulla, Oaks, Brietta M, Arimond, Mary, and Dewey, Kathryn G

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Pediatric, Clinical Trials and Supportive Activities, Clinical Research, Nutrition, Hematology, 3.3 Nutrition and chemoprevention, Prevention of disease and conditions, and promotion of well-being, Reproductive health and childbirth, Adult, Dietary Supplements, Female, Folic Acid, Ghana, Humans, Infant, Infant Nutritional Physiological Phenomena, Infant, Newborn, Iron, Lipids, Male, Maternal Nutritional Physiological Phenomena, Micronutrients, Pregnancy, Young Adult, micronutrient supplementation, iron and folic acid, multiple micronutrient supplements, small-quantity lipid-based nutrient supplements, infants, Animal Production, Food Sciences, Nutrition & Dietetics, Animal production, Food sciences, Nutrition and dietetics
Abstract

BackgroundInterventions are needed to address iron deficiency in low-income settings.ObjectiveThis secondary outcome analysis aimed to compare the hemoglobin (Hb) and iron status [zinc protoporphyrin (ZPP)] of children born to women enrolled in the iLiNS-DYAD trial in Ghana.MethodsWomen ≤20 wk pregnant (n = 1320) were assigned to receive 60 mg Fe/d and 400 µg folic acid/d until delivery and placebo thereafter, and no supplementation for infants (IFA group); or multiple micronutrients containing 20 mg Fe/d until 6 mo postpartum and no supplementation for infants (MMN); or small-quantity lipid-based nutrient supplements (SQ-LNSs) containing 20 mg Fe/d until 6 mo postpartum, and SQ-LNSs for infants from 6 to 18 mo of age (LNS). We compared infants' Hb (g/L) and ZPP (µmol/mol heme) at 6 and 18 mo of age.ResultsAt 6 mo of age, groups did not differ in mean ± SD Hb (overall: 113 ± 9.9 g/L) or geometric mean (95% CI) ZPP [overall: 62.6 (60.6, 64.7)]. At 18 mo of age, mean ± SD Hb (overall: 112 ± 10.4 g/L) did not differ significantly between groups, whereas geometric mean (95% CI) ZPP was lower (P = 0.031) in the LNS group [53.9 (50.7, 57.3)] than the IFA [60.4 (56.7, 64.3)] but not the MMN [58.8 (55.6, 62.2)] group. Further, the LNS group, compared with the IFA and MMN groups combined, had a lower prevalence of elevated (>70) ZPP (27.5% compared with 35%; P = 0.02) and a marginally lower prevalence of anemia (38.7% compared with 44.9%; P = 0.06). These results generally remained unchanged when controlling for prespecified covariates or correcting for inflammation.ConclusionsIn this setting, providing SQ-LNSs or multiple micronutrients with 20 mg Fe/d, compared with iron (60 mg/d) and folic acid, to pregnant women does not affect their infants' Hb or iron status at 6 mo of age, but maternal and infant supplementation with SQ-LNSs increases infants' iron status at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT00970866.

Published
2019

12. Metabolite-related dietary patterns and the development of islet autoimmunity

Author

Johnson, Randi K, Vanderlinden, Lauren, DeFelice, Brian C, Kechris, Katerina, Uusitalo, Ulla, Fiehn, Oliver, Sontag, Marci, Crume, Tessa, Beyerlein, Andreas, Lernmark, Åke, Toppari, Jorma, Ziegler, Anette-G, She, Jin-Xiong, Hagopian, William, Rewers, Marian, Akolkar, Beena, Krischer, Jeffrey, Virtanen, Suvi M, and Norris, Jill M

Subjects
Prevention, Pediatric, Nutrition, Diabetes, Autoimmune Disease, Metabolic and endocrine, Autoantibodies, Autoimmunity, Case-Control Studies, Child, Child Nutritional Physiological Phenomena, Child, Preschool, Diabetes Mellitus, Type 1, Early Diagnosis, Female, Follow-Up Studies, Humans, Infant, Islets of Langerhans, Lipid Metabolism, Male, Metabolomics, Risk Factors, TEDDY Study Group
Abstract

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts.

Published
2019

13. The association of gut microbiota characteristics in Malawian infants with growth and inflammation

Author

Kamng’ona, Arox W, Young, Rebecca, Arnold, Charles D, Kortekangas, Emma, Patson, Noel, Jorgensen, Josh M, Prado, Elizabeth L, Chaima, David, Malamba, Chikondi, Ashorn, Ulla, Fan, Yue-Mei, Cheung, Yin B, Ashorn, Per, Maleta, Kenneth, and Dewey, Kathryn G

Subjects
Infant Mortality, Pediatric, Nutrition, Oral and gastrointestinal, Adult, Body Size, Body Weight, Female, Gastrointestinal Microbiome, Growth and Development, Humans, Infant, Inflammation, Malawi, Male
Abstract

We tested the hypotheses that a more mature or diverse gut microbiota will be positively associated with infant growth and inversely associated with inflammation. We characterized gut microbiota from the stool samples of Malawian infants at 6 mo (n = 527), 12 mo (n = 632) and 18 mo (n = 629) of age. Microbiota diversity and maturity measurements were based on Shannon diversity index and microbiota for age Z-score (MAZ), respectively. Growth was calculated as change in Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HCZ) from 6 to 12 mo and 12 to 18 mo. Biomarkers of inflammation (alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) were measured at 6 and 18 mo. Multivariable models were used to assess the association of each independent variable with each outcome. Microbiota diversity and maturity were related to growth in weight from 6 to 12 mo, but not to growth in length or head circumference or to growth from 12 to 18 mo. Microbiota diversity and maturity may also be linked to inflammation, but findings were inconsistent.

Published
2019

14. Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial

Author

Schiffmann, Raphael, Bichet, Daniel G, Jovanovic, Ana, Hughes, Derralynn A, Giugliani, Roberto, Feldt-Rasmussen, Ulla, Shankar, Suma P, Barisoni, Laura, Colvin, Robert B, Jennette, J Charles, Holdbrook, Fred, Mulberg, Andrew, Castelli, Jeffrey P, Skuban, Nina, Barth, Jay A, and Nicholls, Kathleen

Subjects
Rare Diseases, Neurodegenerative, Clinical Research, Brain Disorders, Digestive Diseases, Clinical Trials and Supportive Activities, Emerging Infectious Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 1-Deoxynojirimycin, Adolescent, Adult, Aged, Biomarkers, Diarrhea, Fabry Disease, Female, Humans, Kidney, Male, Middle Aged, Mutation, Trihexosylceramides, Young Adult, Amenable mutation, Fabry disease, GSRS, Gastrointestinal, Globotriaosylceramide, Lyso-Gb3, Migalastat, Pharmacological chaperone, Other Medical and Health Sciences, Genetics & Heredity
Abstract

BackgroundFabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with amenable mutations.MethodsWe evaluated minimal clinically important differences (MCID) in diarrhea based on the corresponding domain of the patient-reported Gastrointestinal Symptom Rating Scale (GSRS) in patients with Fabry disease and amenable mutations (N = 50) treated with migalastat 150 mg every other day or placebo during the phase 3 FACETS trial (NCT00925301).ResultsAfter 6 months, significantly more patients receiving migalastat versus placebo experienced improvement in diarrhea based on a MCID of 0.33 (43% vs 11%; p = .02), including the subset with baseline diarrhea (71% vs 20%; p = .02). A decline in kidney peritubular capillary globotriaosylceramide inclusions correlated with diarrhea improvement; patients with a reduction > 0.1 were 5.6 times more likely to have an improvement in diarrhea than those without (p = .031).ConclusionsMigalastat was associated with a clinically meaningful improvement in diarrhea in patients with Fabry disease and amenable mutations. Reductions in kidney globotriaosylceramide may be a useful surrogate endpoint to predict clinical benefit with migalastat in patients with Fabry disease.Trial registrationNCT00925301 ; June 19, 2009.

Published
2018

15. Association between breast milk intake at 9–10 months of age and growth and development among Malawian young children

Author

Kumwenda, Chiza, Hemsworth, Jaimie, Phuka, John, Ashorn, Ulla, Arimond, Mary, Maleta, Kenneth, Prado, Elizabeth L, Haskell, Marjorie J, Dewey, Kathryn G, and Ashorn, Per

Subjects
Prevention, Nutrition, Clinical Trials and Supportive Activities, Breast Cancer, Infant Mortality, Cancer, Clinical Research, Pediatric, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Body Mass Index, Body Weight, Breast Feeding, Child Development, Female, Humans, Infant, Malawi, Male, Milk, Human, Motor Skills, Prospective Studies, Single-Blind Method, Socioeconomic Factors, breast milk intake, growth and development, infant, lipid-based nutrient supplements, Nutrition and Dietetics, Nutrition & Dietetics
Abstract

World Health Organization recommends exclusive breastfeeding for infants for the first 6 months of life, followed by introduction of nutritious complementary foods alongside breastfeeding. Breast milk remains a significant source of nourishment in the second half of infancy and beyond; however, it is not clear whether more breast milk is always better. The present study was designed to determine the association between amount of breast milk intake at 9-10 months of age and infant growth and development by 12-18 months of age. The study was nested in a randomized controlled trial conducted in Malawi. Regression analysis was used to determine associations between breast milk intake and growth and development. Mean (SD) breast milk intake at 9-10 months of age was 752 (244) g/day. Mean (SD) length-for-age z-score at 12 months and change in length-for-age z-score between 12 and 18 months were -1.69 (1.0) and -0.17 (0.6), respectively. At 18 months, mean (SD) expressive vocabulary score was 32 (24) words and median (interquartile range) skills successfully performed for fine, gross, and overall motor skills were 21 (19-22), 18 (16-19), and 38 (26-40), respectively. Breast milk intake (g/day) was not associated with either growth or development. Proportion of total energy intake from breast milk was negatively associated with fine motor (β = -0.18, p = .015) but not other developmental scores in models adjusted for potential confounders. Among Malawian infants, neither breast milk intake nor percent of total energy intake from breast milk at 9-10 months was positively associated with subsequent growth between 12 and 18 months, or development at 18 months.

Published
2018

16. Willingness to pay for small‐quantity lipid‐based nutrient supplements for women and children: Evidence from Ghana and Malawi

Author

Adams, Katherine P, Vosti, Stephen A, Ayifah, Emmanuel, Phiri, Thokozani E, Adu‐Afarwuah, Seth, Maleta, Kenneth, Ashorn, Ulla, Arimond, Mary, and Dewey, Kathryn G

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Pediatric, Nutrition, Zero Hunger, Adult, Child, Preschool, Dietary Supplements, Female, Ghana, Humans, Infant, Lipids, Longitudinal Studies, Malawi, Male, Micronutrients, Patient Acceptance of Health Care, Pregnancy, demand, small-quantity lipid-based nutrient supplements, willingness to pay, Nutrition & Dietetics, Nutrition and dietetics, Midwifery
Abstract

Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to enrich maternal and child diets with the objective of preventing undernutrition during the first 1,000 days. Scaling up the delivery of supplements such as SQ-LNS hinges on understanding private demand and creatively leveraging policy-relevant factors that might influence demand. We used longitudinal stated willingness-to-pay (WTP) data from contingent valuation studies that were integrated into randomized controlled nutrition trials in Ghana and Malawi to estimate private valuation of SQ-LNS during pregnancy, postpartum, and early childhood. We found that average stated WTP for a day's supply of SQ-LNS was more than twice as high in Ghana than Malawi, indicating that demand for SQ-LNS (and by extension, the options for effective delivery of SQ-LNS) may be very context specific. We also examined factors associated with WTP, including intervention group, household socioeconomic status, birth outcomes, child growth, and maternal and child morbidity. In both sites, WTP was consistently negatively associated with household food insecurity, indicating that subsidization might be needed to permit food insecure households to acquire SQ-LNS if it is made available for purchase. In Ghana, WTP was higher among heads of household than among mothers, which may be related to control over household resources. Personal experience using SQ-LNS was not associated with WTP in either site.

Published
2018

17. Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso

Author

Prado, Elizabeth L, Abbeddou, Souheila, Adu‐Afarwuah, Seth, Arimond, Mary, Ashorn, Per, Ashorn, Ulla, Bendabenda, Jaden, Brown, Kenneth H, Hess, Sonja Y, Kortekangas, Emma, Lartey, Anna, Maleta, Kenneth, Oaks, Brietta M, Ocansey, Eugenia, Okronipa, Harriet, Ouédraogo, Jean Bosco, Pulakka, Anna, Somé, Jérôme W, Stewart, Christine P, Stewart, Robert C, Vosti, Stephen A, Jimenez, Elizabeth Yakes, and Dewey, Kathryn G

Subjects
Prevention, Pediatric, Clinical Research, Patient Safety, Nutrition, Behavioral and Social Science, 2.3 Psychological, social and economic factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Burkina Faso, Child Development, Child Rearing, Child, Preschool, Female, Ghana, Hemoglobins, Humans, Infant, Iron, Language Development, Malawi, Male, Maternal Health, Models, Statistical, Prospective Studies, Language development, motor development, risk factors, low- and middle-income countries, stimulation, nutrition, growth, lipid-based nutrient supplements, iLiNS Project, Clinical Sciences, Psychology, Cognitive Sciences, Developmental & Child Psychology
Abstract

BackgroundPrevious reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.MethodsWe conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n = 1,023), Malawi (n = 675 and 1,385), and Burkina Faso (n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD.ResultsOut of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts.ConclusionsKey elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status.

Published
2017

18. Impact of small quantity lipid‐based nutrient supplements on infant and young child feeding practices at 18 months of age: results from four randomized controlled trials in Africa

Author

Arimond, Mary, Abbeddou, Souheila, Kumwenda, Chiza, Okronipa, Harriet, Hemsworth, Jaimie, Jimenez, Elizabeth Yakes, Ocansey, Eugenia, Lartey, Anna, Ashorn, Ulla, Adu‐Afarwuah, Seth, Vosti, Stephen A, Hess, Sonja Y, and Dewey, Kathryn G

Subjects
Pediatric, Nutrition, Burkina Faso, Diet, Dietary Fats, Dietary Supplements, Female, Ghana, Humans, Infant, Infant Nutritional Physiological Phenomena, Malawi, Male, Malnutrition, Micronutrients, Nutrition Policy, Nutritional Status, Risk Factors, Sample Size, Zinc, Africa, breastfeeding, feeding practices, infant, nutrient supplements, young child, Nutrition and Dietetics, Nutrition & Dietetics
Abstract

Optimal infant and young child feeding (IYCF) practices can help ensure nutrient adequacy and support healthy growth and development. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been proposed to help fill nutrient gaps, but little is known about the impact of provision of SQ-LNS on breastfeeding or complementary feeding practices. In the context of four coordinated randomized controlled nutrient supplementation trials in diverse sites in Africa, we compared IYCF practices at infant age 18 months (after 9-12 months of supplementation) between those receiving and not receiving SQ-LNS. Practices were assessed by caregiver recall. Continued breastfeeding ranged from 74% (Ghana site) to 97% (Burkina Faso site) and did not differ between groups in any site; prevalence of frequent breastfeeding also did not differ. In two sites (Burkina Faso and Malawi), infants receiving SQ-LNS were more likely to meet the World Health Organization recommendations for frequency of feeding (percentage point differences of 12-14%, P

Published
2017

19. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study

Author

Hughes, Derralynn A, Nicholls, Kathleen, Shankar, Suma P, Sunder-Plassmann, Gere, Koeller, David, Nedd, Khan, Vockley, Gerard, Hamazaki, Takashi, Lachmann, Robin, Ohashi, Toya, Olivotto, Iacopo, Sakai, Norio, Deegan, Patrick, Dimmock, David, Eyskens, François, Germain, Dominique P, Goker-Alpan, Ozlem, Hachulla, Eric, Jovanovic, Ana, Lourenco, Charles M, Narita, Ichiei, Thomas, Mark, Wilcox, William R, Bichet, Daniel G, Schiffmann, Raphael, Ludington, Elizabeth, Viereck, Christopher, Kirk, John, Yu, Julie, Johnson, Franklin, Boudes, Pol, Benjamin, Elfrida R, Lockhart, David J, Barlow, Carrolee, Skuban, Nina, Castelli, Jeffrey P, Barth, Jay, and Feldt-Rasmussen, Ulla

Subjects
Pediatric, Neurodegenerative, Clinical Trials and Supportive Activities, Rare Diseases, Clinical Research, Orphan Drug, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 1-Deoxynojirimycin, Administration, Oral, Adolescent, Adult, Aged, Enzyme Replacement Therapy, Fabry Disease, Female, Humans, Lysosomes, Male, Middle Aged, Molecular Chaperones, Treatment Outcome, alpha-Galactosidase, Fabry disease, Pharmacological chaperone, enzyme replacement therapy, lyso-Gb3, lysosomal storage disorder, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

BackgroundFabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking.MethodsThe main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously treated with ERT. Effects on heart, disease substrate, patient-reported outcomes (PROs) and safety were also assessed.ResultsFifty-seven adults (56% female) receiving ERT (88% had multiorgan disease) were randomised (1.5:1), based on a preliminary cell-based assay of responsiveness to migalastat, to receive 18 months open-label migalastat or remain on ERT. Four patients had non-amenable mutant forms of α-Gal based on the validated cell-based assay conducted after treatment initiation and were excluded from primary efficacy analyses only. Migalastat and ERT had similar effects on renal function. Left ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m2 (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated.ConclusionsMigalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.Trial registration numberNCT00925301; Pre-results.

Published
2017

20. Factors associated with breast milk intake

Author

Kumwenda, Chiza, Hemsworth, Jaimie, Phuka, John, Arimond, Mary, Ashorn, Ulla, Maleta, Kenneth, Ashorn, Per, Haskell, Marjorie J, and Dewey, Kathryn G

Subjects
Prevention, Pediatric, Clinical Research, Nutrition, Infant Mortality, Cancer, Clinical Trials and Supportive Activities, Breast Cancer, Cardiovascular, Metabolic and endocrine, Reproductive health and childbirth, Adolescent, Adult, Body Mass Index, Body Weight, Breast Feeding, Diet, Dietary Supplements, Female, Humans, Infant, Malawi, Male, Milk, Human, Rural Population, Sample Size, Socioeconomic Factors, Young Adult, infant, breast milk intake, lipid-based nutrient supplements, deuterium oxide, dietary intake assessment, Nutrition and Dietetics, Nutrition & Dietetics
Abstract

Exclusive breastfeeding is recommended during the first 6 months of life; thereafter, continued breastfeeding along with nutritious complementary foods is recommended. Continued breastfeeding contributes a substantial proportion of nutrient needs and promotes healthy growth and development, but the quantity of breast milk consumed may be highly variable and little is known about the factors associated with breast milk intake after 6 months of age. The present study was conducted to assess factors associated with breast milk intake of Malawian infants at 9-10 months of age. Breast milk intake was measured using the dose-to-mother deuterium oxide dilution method in a subsample of 358 Malawian infants who were participating in a randomized controlled trial of lipid-based nutrient supplements. Regression analysis was used to assess associations between breast milk intake and several maternal and infant variables. Mean (standard deviation) breast milk intake was 752 (244) g day(-1) . In multiple regression, breast milk intake was positively associated with infant weight (+62 g per kg body weight, P

Published
2016

21. Small-quantity, lipid-based nutrient supplements provided to women during pregnancy and 6 mo postpartum and to their infants from 6 mo of age increase the mean attained length of 18-mo-old children in semi-urban Ghana: a randomized controlled trial 1 , 2

Author

Adu-Afarwuah, Seth, Lartey, Anna, Okronipa, Harriet, Ashorn, Per, Peerson, Janet M, Arimond, Mary, Ashorn, Ulla, Zeilani, Mamane, Vosti, Stephen, and Dewey, Kathryn G

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Nutrition and Dietetics, Pediatric Research Initiative, Pediatric, Clinical Research, Nutrition, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Reproductive health and childbirth, Zero Hunger, Adult, Body Height, Child Development, Dietary Fats, Dietary Supplements, Double-Blind Method, Female, Fetal Development, Fetal Growth Retardation, Ghana, Growth Disorders, Humans, Infant Nutrition Disorders, Infant Nutritional Physiological Phenomena, Infant, Newborn, Lactation, Male, Maternal Nutritional Physiological Phenomena, Micronutrients, Pregnancy, Pregnancy Trimester, First, Prevalence, Risk, Suburban Health, lipid-based nutrient supplements, child growth, home fortification, multiple micronutrients, supplementation, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundChildhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life.ObjectiveWe evaluated the efficacy of small-quantity, lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age.DesignIn this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age.ResultsAt endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and -0.83, respectively, and 12% of the children were stunted (LAZ

Published
2016

22. The effect of providing lipid-based nutrient supplements on morbidity in rural Malawian infants and young children: a randomized controlled trial

Author

Bendabenda, Jaden, Alho, Lotta, Ashorn, Ulla, Cheung, Yin Bun, Dewey, Kathryn G, Vosti, Stephen A, Phuka, John, Maleta, Kenneth, and Ashorn, Per

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition, Rare Diseases, Clinical Research, Clinical Trials and Supportive Activities, Infectious Diseases, Pediatric, Prevention of disease and conditions, and promotion of well-being, 3.3 Nutrition and chemoprevention, Infection, Good Health and Well Being, Child, Preschool, Dietary Supplements, Female, Humans, Infant, Lipids, Malawi, Male, Morbidity, Rural Population, Lipid-based nutrient supplements, Infectious disease morbidity, Iron, Children, Low-income countries, Medical and Health Sciences, Nutrition & Dietetics, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveSafety of home fortificants in children is uncertain in areas where infections are common. We tested the hypothesis that provision of lipid-based nutrient supplements (LNS) containing Fe does not increase infectious morbidity in children.DesignRandomized controlled trial. Infants were randomised to receive 10, 20 or 40 g LNS/d; or no supplement until age 18 months. All LNS contained 6 mg Fe/d. Morbidity outcomes (serious adverse events, non-scheduled visits and guardian-reported morbidity episodes) were compared between control and intervention groups using a non-inferiority margin of 20 %.SettingNamwera and Mangochi catchment areas in rural Malawi.SubjectsInfants aged 6 months (n 1932).ResultsThe enrolled 1932 infants contributed 1306 child-years of follow-up. Baseline characteristics were similar across groups. Compared with the control group, the relative risk (95 % CI) of serious adverse events was 0·71 (0·48, 1·07), 0·67 (0·48, 0·95) and 0·91 (0·66, 1·25) in 10, 20 and 40 g LNS/d groups, respectively. The incidence rate ratio (95 % CI) of non-scheduled visits due to malaria was 1·10 (0·88, 1·37), 1·08 (0·89, 1·31) and 1·21 (1·00, 1·46), and of guardian-reported morbidity episodes was 1·04 (0·96, 1·11), 1·03 (0·97, 1·10) and 1·04 (0·97, 1·10), in the respective LNS groups.ConclusionsProvision of 10 and 20 g LNS/d containing 6 mg Fe/d did not increase morbidity in the children. Provision of 40 g LNS/d did not affect guardian-reported illness episodes but may have increased malaria-related non-scheduled visits.

Published
2016

23. Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants 2–4

Author

Dashti, Hassan S, Follis, Jack L, Smith, Caren E, Tanaka, Toshiko, Cade, Brian E, Gottlieb, Daniel J, Hruby, Adela, Jacques, Paul F, Lamon-Fava, Stefania, Richardson, Kris, Saxena, Richa, Scheer, Frank AJL, Kovanen, Leena, Bartz, Traci M, Perälä, Mia-Maria, Jonsson, Anna, Frazier-Wood, Alexis C, Kalafati, Ioanna-Panagiota, Mikkilä, Vera, Partonen, Timo, Lemaitre, Rozenn N, Lahti, Jari, Hernandez, Dena G, Toft, Ulla, Johnson, W Craig, Kanoni, Stavroula, Raitakari, Olli T, Perola, Markus, Psaty, Bruce M, Ferrucci, Luigi, Grarup, Niels, Highland, Heather M, Rallidis, Loukianos, Kähönen, Mika, Havulinna, Aki S, Siscovick, David S, Räikkönen, Katri, Jørgensen, Torben, Rotter, Jerome I, Deloukas, Panos, Viikari, Jorma SA, Mozaffarian, Dariush, Linneberg, Allan, Seppälä, Ilkka, Hansen, Torben, Salomaa, Veikko, Gharib, Sina A, Eriksson, Johan G, Bandinelli, Stefania, Pedersen, Oluf, Rich, Stephen S, Dedoussis, George, Lehtimäki, Terho, and Ordovás, José M

Subjects
Aging, Sleep Research, Obesity, Prevention, Nutrition, Genetics, Neurosciences, Behavioral and Social Science, Oral and gastrointestinal, Cardiovascular, Metabolic and endocrine, Cancer, Adult, Body Mass Index, CLOCK Proteins, Cohort Studies, Cross-Sectional Studies, Diet, Dietary Proteins, Energy Intake, Fatty Acids, Unsaturated, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Sleep, White People, Young Adult, CLOCK, circadian rhythm, dietary intake, gene-environment interaction, sleep duration, gene-environment, interaction, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundShort sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake.ObjectivesWe examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations.DesignWe conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.ResultsWe observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake.ConclusionsOur results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile.

Published
2015

24. 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, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Kirsten Beadon, Philip Beak, Andy Beale, Kathy Beard, Jack Bearpark, Alanna Beasley, Sandee Beattie, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Sarah Beckley, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Sophia Beeby, Gail Beech, Michelle Beecroft, Nigel Beer, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Jessica Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer Bellamu, Mary Bellamy, Tammy Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Sarah Benkenstein, Tracey Benn, Ann Bennett, Caroline Bennett, Denise Bennett, Gillian Bennett, Kaytie Bennett, Kristopher Bennett, Lorraine Bennett, Miriam R Bennett, Sara Bennett, Karen Bennion, Gautham Benoy, Vivienne Benson, Andrew Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Frida Best, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Lila Nath Bhandari, Sangam Bhandari, Jennifer Bhanich Supapol, Aashutosh Bhanot, Ravina Bhanot, Swati Bhasin, Abdul Bhat, Prashanth Bhat, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Parminder Bhuie, M S Bhuiyan, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Prof Binh, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Sarah Bird, Mark Birt, Claire Bishop, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Mustapha Bittaye, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Virginia Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Cameron Blair, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Parry Blaxill, Katie Blaylock, Jane Blazeby, Natalie Blencowe, Ben Bloom, Jack Bloomfield, Angela Bloss, Alex Blowers, Samuel Blows, Hannah Bloxham, Susan Blrd, Louise Blundell, Andrew Blunsum, Mark Blunt, Tadhg Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Kwabena Appiah Boahen, Marilyn Boampoaa, Sarah Board, Boniface Bobie, Karen Bobruk, Pritesh N Bodalia, Neena Bodasing, Marianne Boden, Tanya Bodenham, Gabriele Boehmer, Marta Boffito, Katherine Bohanan, Kristyna Bohmova, Niamh Bohnacker, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed O Bokhari, Idan Bokobza, Ambrose Boles, Clare Bolger, Candice Bonaconsa, Charlotte Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Joseph Bonney, Lizzy Bonney, Lauren Booker, Sarah Boot, Matthew Boothroyd, Joanne Borbone, Naomi Borman, Samantha Bosence, Kirsty Bostock, Neil Botting, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Tarek Boumrah, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Tabitha Bowker, Helen Bowler, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Helen Bowyer, Aileen Boyd, Jenny Boyd, Laura Boyd, Nicola Boyer, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Abbey Bracken, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Clare Brady, Rebecca Brady, Shirin Brady, Pedro Braga Sardo, Denise Braganza, Megan Braithwaite, Susan Brammer, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Sophie Brattan, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Carolin Bresges, Catherine Bressington, Giovanna Bretland, Chris Brewer, Michael Bridgett, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Tracey Brigstock, Lutece Brimfield, Philip Brinksman, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Hannah Britton, Lauren Broad, Sarah Broadhead, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Mary Brodsky, Fiona Brogan, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Deirdre Brooking, Alison Brooks, Daniel Brooks, Jolene Brooks, Karen Brooks, Nicole Brooks, Philip Brooks, Rachel Brooks, Samuel Brooks, Sophie Brooks, Malcolm Broom, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Ammani Brown, Andrew Brown, Ashley Brown, Caitlin Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Jo Brown, Louise Brown, Niall Brown, Nicola Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Andrei Brunchi, Nigel Brunskill, Alan Brunton, Margaret Brunton, Meera Bryant, Emma Bryden, Hannah Brzezicki, April Buazon, Maya H Buch, Ruaridh Buchan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Lisa Buck, Matthew Buckland, Clare Buckley, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, Alex Budds, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Kate Bull, Rhian Bull, Thomas Bull, Emily Bullock, Susan Bullock, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Oliver Burbidge, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Richard Burgess, Sophia Burgess, Erlina Burhan, Hasan Burhan, Hannah Burke, Kerry Burke, Adrian Burman, Sara Burnard, Caroline Burnett, Sharon Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Kiki Burns, Daniel Burrage, Kate Burrows, Claire Burston, Anna Burton, Ben Burton, Fiona Burton, Helen Burton, Matthew Burton, Mannaria Butar butar, Deborah Butcher, Aaron Butler, Emily Butler, Jessica Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Jenny Butler, Al-Tahoor Butt, Massawer Butt, Mohammad M Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Hannah Bye, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Amanda Cabandugama, Luisa Cabrero, Simone Caddy, Ruth Cade, Anthony Cadwgan, Zhen Cahilog, Ajeng Cahyareny, Donna Cairney, James Calderwood, Darren Caldow, Emily Cale, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Karen Campbell, Marion Campbell, Mark Campbell, Rachael Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Lisa Canclini, Shaula M Candido, Janie Candlish, Cielito Caneja, Alexandra Cann, Johnathon Cann, Ruby Cannan, Abigail Cannon, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Ebnier Canonizado, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Richard Capstick, Thomas Capstick, Catalin Caraenache, Aimee Card, Mary Cardwell, Charles Carey, Rachel Carey, Simon Carley, Ffion Carlin, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Jodi Carpenter, Sharon Carr, Anna Carrasco, Zoe Carrington, Amy Carroll, Anne Carroll, Paul Carroll, Rachel Carson, Cindy Cart, Emma Carter, Jonathan Carter, Michael Carter, Natasha Carter, Paul Carter, Penny Carter, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Lotoyah Carty, Jaime Carungcong, Charlotte Carver, Emma Carver, Rachel Carver, Susan Casey, Annie Cassells, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Anelise Catelan Zborowski, Susanne Cathcart, Katrina Cathie, Darwin Catibog, Christine Catley, Laura Catlow, Matthew Caudwell, Anna Cavazza, Ashleigh Cave, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Kay Cawthorne, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, Cyril J Chacko, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, Petya Chalakova, Bimal Sharma Chalise, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Jay Marie Chan, Kawai Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H S Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Yvonne Chang, Ho Quang Chanh, Grace Chaplin, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Matthew Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Sam Charlton, Kevin Chatar, Calvin Chatha, Debra Chatterton, Ritesh Chaube, Muhammad Y N Chaudhary, Netra B Chaudhary, Iram Chaudhry, Zain Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi S Chauhan, Alexander Chavasse, Nicola Chavasse, Vipal Chawla, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Floria Cheng, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Mary Cherrie, Helen Cheshire, Chee Kay Cheung, Elaine Cheung, Kayan Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Moses Chikungwa, Zviedzo A Chikwanha, Gemma Chilcott, Sam Chilcott, Alison Chilvers, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Ezomike Chinonso, Chloe Chin-Saad, Margaret Chirgwin, Heather Chisem, Claire Chisenga, Catherine Chisholm, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Laura Chiverton, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Meena Chopra, Michelle Chopra, Vandana Choudhary, Omur Choudhury, Sarah Choudhury, Bing-Lun Chow, Mahibbur Chowdhury, Shahid Chowdhury, Angela Chrisopoulou, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Georgios Christoforou, Thereza Christopherson, Anna Christou, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Yee Chung, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Bridget Clancy, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Emma Clark, Felicity Clark, Gabrielle Clark, James Clark, Julia Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Martyn Clark, Matthew Clark, Nicola Clark, Patricia Clark, Richard Clark, Thomas Clark, Tonia Clark, Zoe Clark, Alison Clarke, Andrea Clarke, Jude Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Louis Claxton, Kate Clay, Catherine Clayton, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Bethan Clearyb, Chris Cleaver, Rose Cleeton, Ian Clement, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Sue Clenton, Sheryl Cliff, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Vincent Clubb, Samantha Clueit, Lisa Clutterbuck, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Laura Cockayne, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, David Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Garry Coleman, Matt Coleman, Nick Coleman, Holly Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Kathleen Collie, Alexandra Collier, Danielle Collier, Dawn Collier, Heather Collier, Terry Collingwood, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Kayleigh Collins, Megan Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Alison Comerford, Dónal Concannon, Alison Condliffe, Robin Condliffe, Emma Connell, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Emma Connor, Antonia Conroy, Kevin Conroy, Veronica Conteh, Rory Convery, Francesca Conway, Grainne Conway, Rhiannon Conway, Robert Conway, Jo-Anna Conyngham, Amanda Cook, Amber Cook, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Martin Cook, Sarah Cook, Danielle Cooke, Graham Cooke, Hannah Cooke, Justin Cooke, Katrina Cooke, Tim Cooke, Vikki Cooke, Adele Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Samantha Cooray, Thomas Cope, Sinead Corbet, Carolyn Corbett, Ailsa Corbishley, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Aisling Corr, Mirella Corredera, Ruth Corrigan, P Corry, Rita Corser, Jon Cort, Denise Cosgrove, Tracey Cosier, Patricia Costa, Telma Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, George Couch, Martina Coulding, Andrew Coull, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Amanda J Coutts, Alexander Cowan, Elena Cowan, Richard Cowan, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Emma Cox, Giles Cox, Helen Cox, Karina Cox, Miriam Cox, Karen Coy, Andrea Cradduck-Bamford, Hannah Craig, Jayne Craig, John Craig, Victoria Craig, Felicity Craighead, Matthew Cramp, Hayley Cranston, Sheetal S Crasta, Jacolene Crause, Angie Crawford, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Amanda Creaser-Myers, Joanne Cremona, Saveria Cremona, Anna Crepet, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Jennifer Crooks, Harriet Crosby, Elizabeth Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Lorraine Cullen, Gillian Cummings-Fosong, Victoria Cunliffe, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Susan Currie, Susie Currie, Jonathan Curtis, Katrina Curtis, Matthew Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Jennifer Cuthill, Sean Cutler, Sarah Cutts, Marta Czekaj, Patrycja Czylok, Shane D'Souza, Joana da Rocha, Mohammed Dafalla, Andrew Dagens, Helen Daggett, Jacqui Daglish, Sandeep Dahiya, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Susan Dale, Jolyon Dales, Umberto D'Alessandro, Helen Dalgleish, Helen Dallow, Carlo D'aloia, Dermot Dalton, Morag Dalton, Zoe Daly, Mansi Damani, Eleanor Damm, Akila Danga, Joanne Dangerfield, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Kwaku Gyasi Danso, Sandra Danso-Bamfo, Quang Tung Dao, Suzanne Darby, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Kate Darlington, Sarah Darnell, Thomas Darton, Guledew Darylile, Avisnata Das, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Vaishali Dave, Emily Davenport, Mark Davey, Miriam Davey, Molly Davey, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Alison Davies, Amanda Davies, Amy Davies, Angela Davies, Bethan Davies, Caroline Davies, Carolyn Davies, Catrin Davies, Dawn Davies, Drew Davies, Elaine Davies, Elinor Davies, Ellie Davies, Ffyon Davies, Gwyneth Davies, Helen Davies, Jennifer Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Llinos Davies, Louisa Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sally Davies, Sarah Davies, Simon Davies, Sue Davies, Alison Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Andrea Davis-Cook, Alexander Davison, Christine Dawe, H Dawe, Mark Dawkins, Angela Dawson, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Lucinda Dawson, Mike Dawson, Susan Dawson, Tom Dawson, Isla Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy N Day, Jamie D'Costa, Parijat De, Pradip De, Duneesha de Fonseka, Toni de Freitas, Pamela De Los Santos Dominguez, Roberta De Pretto, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Phillip De Souza, Anthony De Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Gonzalo De-La-Cedra, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Alexandra Dent, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Usha Devkota, Debbie Devonport, Matthew Devonport, Prakash Dey, Vishal Dey, Rogin Deylami, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Ankush Dhariwal, Dawpadee Dharmasena, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Syra Dhillon, Meghnath Dhimal, Dipali Dhiru, Trupti Dhorajiwala, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Mohammed Dibas, Debbie Dickerson, Pamela Dicks, Matt Dickson, Stuart Dickson, J Digby, Ronneil Digpal, Sean Dillane, Sarah Diment, Paul Dimitri, Georgios Dimitriadis, Sajeel Din, Thai H Dinh, Thi T T Dinh, Alex Dipper, Sabiq Dipro, Laura Dirmantaite, Lorelle Dismore, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Preeti Diwan, Caroline Dixon, Giles Dixon, Kate Dixon, Brice Djeugam, Sipho Dlamini, Petr Dlouhy, Andrea D'Mello, Paul Dmitri, Thi Tien Do, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, Jacqueline Dodd, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Conor Doherty, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Katie Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Phu Khiem Dong, Martha Donkor, Sinead Donlon, Joanne Donnachie, Eilish Donnelly, Ronan Donnelly, Phil Donnison, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Emma Dooks, Reece J Doonan, Rogier Van Doorn, Grainne Doran, Rachael Dore, Kane Dorey, Sharon Dorgan, Kataryna Dos Santos, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Isabelle Doss, Theonymfi Doudouliaki, Andrew Dougherty, Jill Doughty, Katie Douglas, Jonathan Douse, Allyn Dow, Lucy Dowden, Michelle Dower, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Robert Downey, Caroline Downing, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Anthony Drexel, Celine Driscoll, Helena Drogan, Odysseas Drosos, Graham Drummond, Katie Drury, Kay Druryk, Ronald Druyeh, Jack Dryburgh-Jones, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Stephen Duberley, Paige K Duckenfield, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Heather Duffy, Helen Duffy, Katharine Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Rauand Duhoky, Janice Duignan, Jennifer Dulay, Simon Dummer, Alexis Duncan, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, Holly Duncan, Robert Duncan, Stephanie Dundas, Do Van Dung, Aileen Dunleavy, Julia Dunleavy, Alessia Dunn, Charlotte Dunn, Damian Dunn, Laura Dunn, Paul Dunn, Charlene Dunne, Karen Dunne, Fiona Dunning, Aidan Dunphy, Tran Thi Hai Duong, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Leanne Durdle, Natalie Duric, Alison Durie, Emily Durie, Samuel Durogbola, Chris Durojaiye, Laura Durrans, Katie Durrant, Hannah Durrington, Iheukwumere Duru, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Dennis Dwomoh Nkrumah, Ellen Dwyer, Zara Dyar, Claudia Dyball, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Lauren Eadie, Rebekah Eadie, Laura Eagles, Beena Eapen, Naomi Earl, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Amy Easthope, Fraser Easton, Jack Easton, Patrick Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Alison Eccles, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Mary Edmondson, Tracy Edmunds, Abby Edwards, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Martin Edwards, Sophie Edwards, Jenny Eedle, Aline Eggink, Dawn Egginton, Sam Eggleston, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Nagla Elashhar, Lisa Elawamy, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Emma Eldridge, Diana Eleanor, Uchenna Elenwa, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Mohamed A A Elhadi, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura N Ellerton, Lucy Elliot, Amy Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Sian Elliott, Annie Ellis, Christine Ellis, Kaytie Ellis, Leila Ellis, Rupert Ellis, 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 Gore, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Maria Gorniok, Diana Gorog, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Nicole Gould, Susan Gould, Charlotte Goumalatsou, Lysander Gourbault, Abha Govind, Rajesh Govindan, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Cheryl Graham, Clive Graham, Jonathan Graham, Justin Graham, Libby Graham, Rachel Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Kirstie Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Glaxy Gray, Jackie Gray, Karen Gray, Nicola Gray, Roxanne Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Amy Green, Amy S Green, Charlotte Green, 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, 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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, 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McCann, Erin McCann, Alexandra McCarrick, Brendan McCarron, Eoghan McCarthy, Michelle McCarthy, Natalie McCarthy, Sinead McCaughey, Tara McClay, Beverley McClelland, Declan McClintock, Michael McCloskey, Kirsten McCollum, Alasdair McCorkindale, Patricia McCormack, Jacqueline McCormick, Jake McCormick, Wendy McCormick, Paul McCourt, Jame McCrae, Sharon McCready, Gordan McCreath, Helen McCreedy, Claire McCue, Iain J McCullagh, Liz McCullagh, Megan McCullagh, Conor McCullough, Katherine McCullough, Nicola McCullough, Sarah McCullough, Fiona McCurrach, John McDermott, Paula McDermott, Rory McDermott, Katharine McDevitt, Helen McDill, Basil McDonald, Carly McDonald, Claire McDonald, Debbie McDonald, Rob McDonald, Sam McDonald, Damhnaic McDonald, Natasha McDonnell, Catherine McDougall, Lilly McDougall, Rowan McDougall, Irene McEleavy, Fred McElwaine, Julie McEntee, Evanna McEvoy, Claire McEwan, Ruth McEwen, Margaret McFadden, Denise McFarland, Margaret McFarland, Rachel McFarland, Joe McFlynn, Erin McGarry, Lorcan McGarvey, Alex McGeachan, Frederick McGee, Laura McGenily, Clodagh McGettigan, Michael McGettrick, Christopher McGhee, Fiona McGill, Sarah McGinnity, Neil McGlinchey, Phil McGlone, Deborah McGlynn, Claire McGoldrick, Clare McGoldrick, Elizabeth McGough, Christopher McGovern, Roisin McGovern, Angela McGowan, Anne McGown, Brendan McGrath, Amanda McGregor, Annemarie McGregor, Michael P McGuigan, Heather McGuinness, Sean McGuire, Tara McHugh, Caroline McInnes, Neil McInnes, Jerome McIntosh, Karen McIntyre, Mhairi McIntyre, Lorna McKay, Conor P McKeag, Jacqueline McKeane, Madeleine McKee, Joseph McKeever, Judith McKenna, Shirley McKenna, Mary McKenzie, Donogh McKeogh, Caroline McKerr, Anthony M McKie, Hayley Mckie, Laura Mckie, Gerard McKnight, Heather McLachlan, Andrew McLaren, Barbara McLaren, Nicola McLarty, Danielle Mclaughlan, Maria McLaughlin, James McLay, Mary McLeish, Tina McLennan, Stewart McLure, Anne Marie McMahon, Genevieve McMahon, Mike McMahon, Stephen McMahon, Terence McManus, Moyra McMaster, P McMaster, Paddy McMaster, Faye Mcmeeken, Samuel McMeekin, Nicola McMillan, Katherine McMillen, Jason McMinn, Liam McMorrow, Heather McMullen, Christopher McMurran, Helen McNally, Fiona McNeela, Lynne McNeil, Claire McNeill, Jessica McNeill, Shea McNeill, Una McNelis, Melanie McNulty, Roisin McNulty, Christopher McParland, Mark McPhail, Alison McQueen, Anna McSkeane, Denise McSorland, Therese McSorley, Gini McTaggart, Jacqueline McTaggart, Joanna Mead, Paul Mead, Emma Meadows, Olivia Meakin, Ben Mearns, Claire Mearns, Kim Mears, William Mears, Manjula Meda, Ayren Mediana, Ross Medine, Thomas Medveczky, Sharon Meehan, Emily Meeks, Abbi Megan, Nevan Meghani, Salim Meghjee, Sharon Megson, Amina Mehar, Mehr N Mehmood, Rohan Mehra, Rohan Mehta, Graeme Meintjes, James Meirill, James Meiring, Rayane Mejri, Ellen Mekonnen, Sabina Melander, Adriana-Stefania Melinte, Jennifer Mellersh, Lucy Melling, Christie Mellish, Francesca Mellor, Joe S 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Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Omaisa Mushtaq, Sohmal Musini, Ahmed M M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Naveed Mustfa, Zhain Mustufvi, Callum Mutch, Rachel Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, James S Myerson, Khin Swe Myint, Yadee Myint, Georgina Mynott, Libor Myslivecek, Patricia Nabayego, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Behzad Nadjm, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Widya Naftalia, Thapas Nagarajan, Leah Naglik, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Deborah Nakiboneka-Ssenabulya, Sri Nallapareddy, Soum 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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
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25. Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

Author

Ellinghaus, David, Zhang, Hu, Zeissig, Sebastian, Lipinski, Simone, Till, Andreas, Jiang, Tao, Stade, Björn, Bromberg, Yana, Ellinghaus, Eva, Keller, Andreas, Rivas, Manuel A, Skieceviciene, Jurgita, Doncheva, Nadezhda T, Liu, Xiao, Liu, Qing, Jiang, Fuman, Forster, Michael, Mayr, Gabriele, Albrecht, Mario, Häsler, Robert, Boehm, Bernhard O, Goodall, Jane, Berzuini, Carlo R, Lee, James, Andersen, Vibeke, Vogel, Ulla, Kupcinskas, Limas, Kayser, Manfred, Krawczak, Michael, Nikolaus, Susanna, Weersma, Rinse K, Ponsioen, Cyriel Y, Sans, Miquel, Wijmenga, Cisca, Strachan, David P, McArdle, Wendy L, Vermeire, Séverine, Rutgeerts, Paul, Sanderson, Jeremy D, Mathew, Christopher G, Vatn, Morten H, Wang, Jun, Nöthen, Markus M, Duerr, Richard H, Büning, Carsten, Brand, Stephan, Glas, Jürgen, Winkelmann, Juliane, Illig, Thomas, Latiano, Anna, Annese, Vito, Halfvarson, Jonas, D'Amato, Mauro, Daly, Mark J, Nothnagel, Michael, Karlsen, Tom H, Subramani, Suresh, Rosenstiel, Philip, Schreiber, Stefan, Parkes, Miles, and Franke, Andre

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Biotechnology, Genetics, Inflammatory Bowel Disease, Autoimmune Disease, Human Genome, Clinical Research, Digestive Diseases, Crohn's Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Inflammatory and immune system, Adolescent, Adult, Case-Control Studies, Colitis, Ulcerative, Crohn Disease, Exome, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mutation, Missense, Nuclear Proteins, Polymorphism, Single Nucleotide, Positive Regulatory Domain I-Binding Factor 1, Quantitative Trait Loci, Repressor Proteins, Young Adult, Whole-Exome Sequencing, Complex Disease, CD, Crohn’s disease, GWAS, IBD, IFN, NF-κB, PBL, PBMC, SNP, SNV, TLR, Toll-like receptor, UC, WT, eQTL, expression quantitative trait locus, genome-wide association studies, inflammatory bowel disease, interferon, nuclear factor κB, peripheral blood lymphocyte, peripheral blood mononuclear cell, qRT-PCR, quantitative reverse-transcription polymerase chain reaction, single nucleotide polymorphism, single nucleotide variant, ulcerative colitis, wild-type, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsGenome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies.MethodsWe sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems.ResultsWe identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 × 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 × 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor κB activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways.ConclusionsWe have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.

Published
2013

26. A Bivariate Genome-Wide Approach to Metabolic Syndrome STAMPEED Consortium

Author

Kraja, Aldi T, Vaidya, Dhananjay, Pankow, James S, Goodarzi, Mark O, Assimes, Themistocles L, Kullo, Iftikhar J, Sovio, Ulla, Mathias, Rasika A, Sun, Yan V, Franceschini, Nora, Absher, Devin, Li, Guo, Zhang, Qunyuan, Feitosa, Mary F, Glazer, Nicole L, Haritunians, Talin, Hartikainen, Anna-Liisa, Knowles, Joshua W, North, Kari E, Iribarren, Carlos, Kral, Brian, Yanek, Lisa, O’Reilly, Paul F, McCarthy, Mark I, Jaquish, Cashell, Couper, David J, Chakravarti, Aravinda, Psaty, Bruce M, Becker, Lewis C, Province, Michael A, Boerwinkle, Eric, Quertermous, Thomas, Palotie, Leena, Jarvelin, Marjo-Riitta, Becker, Diane M, Kardia, Sharon LR, Rotter, Jerome I, Chen, Yii-Der Ida, and Borecki, Ingrid B

Subjects
Biomedical and Clinical Sciences, Nutrition, Human Genome, Clinical Research, Cardiovascular, Diabetes, Obesity, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Metabolic Syndrome, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

Published
2011

27. Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.

Author

Sovio, Ulla, Bennett, Amanda J, Millwood, Iona Y, Molitor, John, O'Reilly, Paul F, Timpson, Nicholas J, Kaakinen, Marika, Laitinen, Jaana, Haukka, Jari, Pillas, Demetris, Tzoulaki, Ioanna, Molitor, Jassy, Hoggart, Clive, Coin, Lachlan JM, Whittaker, John, Pouta, Anneli, Hartikainen, Anna-Liisa, Freimer, Nelson B, Widen, Elisabeth, Peltonen, Leena, Elliott, Paul, McCarthy, Mark I, and Jarvelin, Marjo-Riitta

Subjects
Humans, Body Height, Prospective Studies, Child Development, Genotype, Polymorphism, Single Nucleotide, Adolescent, Adult, Child, Infant, Newborn, European Continental Ancestry Group, Finland, Female, Male, Genome-Wide Association Study, Infant, Newborn, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p

Published
2009

28. The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease

Author

Cihan Ay, Ingrid Pabinger, Katarina D. Kovacevic, Georg Gelbenegger, Christian Schörgenhofer, Peter Quehenberger, Petra Jilma-Stohlawetz, Raute Sunder-Plassman, James C. Gilbert, Shuhao Zhu, Bernd Jilma, and Ulla Derhaschnig

Subjects
Male, Factor VIII, Platelet Count, von Willebrand Disease, Type 2, Hematology, Hemostatics, Polyethylene Glycols, von Willebrand Diseases, Platelet Glycoprotein GPIb-IX Complex, von Willebrand Factor, Humans, Female, Collagen, Prospective Studies
Abstract

Type 2B von Willebrand disease (VWD) is characterized by an increased binding affinity of von Willebrand factor (VWF) to platelet glycoprotein Ib. This can lead to clearance of high-molecular-weight (HMW) multimers and thrombocytopenia with a resulting moderate-severe bleeding phenotype. Rondoraptivon pegol (BT200) is a pegylated aptamer binding to the A1 domain of VWF with a novel mechanism of action: it enhances VWF/factor VIII (FVIII) levels by decreasing their clearance. To study the potential benefit of rondoraptivon pegol in patients with type 2B VWD, we conducted a prospective phase 2 trial. Patients with type 2B VWD received 3 mg rondoraptivon pegol subcutaneously on study days 1, 4, and 7, followed by 6 to 9 mg every week until day 28. Five patients (male:female ratio = 3:2) were included. Rondoraptivon pegol rapidly tripled platelet counts from a median of 60 to 179 × 10E9/L (P < .001). Circulating VWF antigen increased from a median of 64% to 143%, which doubled FVIII activity levels from 67% to 134%. In all thrombocytopenic patients, plasma levels of VWF:GPIbM normalized, VWF ristocetin cofactor and VWF collagen-binding activity increased, and HMW multimers appeared. These pronounced improvements reversed during washout of the drug, thus demonstrating causality. The A1 domain binding aptamer directly corrects the underlying defect of type 2B VWD, thus providing a novel potential option for prophylaxis and treatment of patients with this VWD type. These data provide the basis for a phase 2b/3 trial in such patients. This trial was registered at www.clinicaltrials.gov as #NCT04677803.

Published
2022
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29. Pituitary function and the response to GH therapy in patients with Langerhans cell histiocytosis: analysis of the KIMS database

Author

Philippe Touraine, Yempabou Sagna, Anders F Mattsson, Pia Burman, André P Van Beek, Martin Ove Carlsson, Ferah Aydin, Ulla Feldt-Rasmussen, Cecilia Camacho-Hübner, and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Adult, Male, Hormone Replacement Therapy, Human Growth Hormone, Endocrinology, Diabetes and Metabolism, General Medicine, Hypopituitarism, Histiocytosis, Langerhans-Cell, Cross-Sectional Studies, Endocrinology, Quality of Life, Humans, Female, Child, Dwarfism, Pituitary
Abstract

Objective To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and −0.5 (−1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (−1.5 to −0.3 (mmol/L); P n = 20) was improved by 2.8 points (−5.6 to 0.0; P 2 (95% CI: −0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported. Conclusion After 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.

Published
2022
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30. Association between thoracic and third lumbar CT-derived muscle mass and density in Caucasian patients without chronic disease:a proof-of-concept study

Author

Mia Solholt Godthaab Brath, Marina Sahakyan, Esben Bolvig Mark, Jens Brøndum Frøkjær, Henrik Højgaard Rasmussen, Lasse Riis Østergaard, and Ulla Møller Weinreich

Subjects
Adult, Male, Muscle, Skeletal/diagnostic imaging, Lumbar Vertebrae/diagnostic imaging, Contrast media, Tomography, X-Ray Computed/methods, Body composition, Tomography (x-ray computed), Chronic Disease, Humans, Muscle (skeletal), Radiology, Nuclear Medicine and imaging, Female, Retrospective Studies
Abstract

Background Computed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease. Methods A proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson’s correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test–retest with SMA as proxy parameters were used. Results Twenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm2, females 118.5 cm2) and SMI (97.8 cm2/m2 and 70.4 cm2/m2, respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890). Conclusions This study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT. Relevance statement In COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation. Key points • Any thoracic level can be used to assess thoracic muscle mass. • Thoracic level 5 is strongly associated with the 3rd lumbar muscle area. • A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index. • Thoracic level 10 is strongly associated with the 3rd lumbar muscle density. Graphical Abstract

Published
2023
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31. Psychiatric Symptoms, Posttraumatic Growth, and Life Satisfaction Among Parents of Seriously Ill Infants: A Prospective Case-Controlled Study

Author

Krista Koivula, Siiri Isokääntä, Kati Tavast, Iines Toivonen, Iina Tuomainen, Merja Kokki, Kirsi Honkalampi, Ulla Sankilampi, and Hannu Kokki

Subjects
Male, Parents, Infant, Newborn, Infant, Mothers, Personal Satisfaction, Anxiety, Stress Disorders, Post-Traumatic, Fathers, Clinical Psychology, Humans, Female, Posttraumatic Growth, Psychological, Stress, Psychological
Abstract

We evaluated psychiatric symptoms, posttraumatic growth, and life satisfaction among the parents (n = 34) of newborns (n = 17) requiring therapeutic hypothermia or urgent surgery (interest group). Our control group included 60 parents of healthy newborns (n = 30). The first surveys were completed soon after diagnosis or delivery and the follow-up surveys 1 year later (participation rate 88% in the interest group and 70% in the control group). General stress was common in both groups but was more prevalent in the interest group as were depressive symptoms, too. Anxiety was more common in the interest group, although it showed a decrease from the baseline in both groups. Life satisfaction had an inverse correlation with all measures of psychiatric symptoms, and it was lower in the interest group in the early stage, but similar at 12 months due to the slight decline in the control group. Mothers in the interest group had more anxiety and depressive symptoms than fathers in the early stage. Mothers had more traumatic distress than fathers at both time points. Half of the parents experienced substantial posttraumatic growth at 12 months. In conclusion, the serious illness of an infant substantially affects the well-being of the parents in the early stages of illness and one year after the illness.

Published
2022
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32. Ocular surface health of the Finnish elderly population

Author

Ulla Aapola, Janika Nättinen, Ilona Suurkuukka, Jaakko Tuomilehto, Sirkka Keinänen‐Kiukaanniemi, Jouko Saramies, Hannu Uusitalo, Tampere University, Clinical Medicine, BioMediTech, Eye Centre, Business Finland, Elsemay Bjorn Fund, Glaukooma Tukisäätiö Lux, Pirkanmaa Regional Fund, and Helsinki University Hospital

Subjects
Male, prevalence, Meibomian Glands, General Medicine, dry eye disease, Ophthalmology, Cross-Sectional Studies, ocular surface disease, Tears, Humans, Female, Dry Eye Syndromes, epidemiology, 3125 Otorhinolaryngology, ophthalmology, Finland, Aged
Abstract

Purpose: The aim of this study was to describe the clinical ocular surface characteristics in a population-based sample of Finnish elderly people. Methods: This cross-sectional study included 601 subjects (335 females, 266 males) born between the years 1933-1956 and living in Savitaipale, Finland. Ocular surface health was evaluated using a comprehensive set of diagnostic tests. Previous dry eye (DE) diagnosis and history of drug treatment of DE were also recorded. Differences between sexes were estimated with Wilcoxon rank sum test and Fisher's exact test. Results: Overall, 10% and 33% of people displayed signs of DE and ocular surface disease (OSD), respectively, and 30% had been previously diagnosed with DE and 36% used some form of drugs for DE. Men displayed more severe signs of meibomian gland dysfunction, blepharitis and conjunctival redness (p < 0.001), while women had higher scores in corneal staining (p = 0.005) and OSD Index (p < 0.001). Conclusion: Signs of OSD and DE are common among the Finnish elderly population. However, the diagnosis is affected by the diagnostic criteria used and significant differences exist between sexes. Although women were more frequently diagnosed with DE and OSD and experienced more ocular surface irritation, men had more often lid and meibomian gland-related issues. The current diagnostic criteria of DE pose a risk of misclassifying men, who commonly display less severe symptoms in comparison with women yet exhibit more severe clinical signs associated especially with the lid margin. This work was supported by Business Finland, Elsemay Bjorn Fund, Glaukooma Tukisäätiö Lux, Pirkanmaa Regional Fund and Competitive State Research Financing of the Expert Responsibility area of Helsinki University Hospital. The funding sources were not involved in study design, data collection, analysis and interpretation, decision to publish or preparation of this article. Sí

Published
2022
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33. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Author

Charles C Wykoff, Francis Abreu, Anthony P Adamis, Karen Basu, David A Eichenbaum, Zdenka Haskova, Hugh Lin, Anat Loewenstein, Shaun Mohan, Ian A Pearce, Taiji Sakamoto, Patricio G Schlottmann, David Silverman, Jennifer K Sun, John A Wells, Jeffrey R Willis, Ramin Tadayoni, Thomas Aaberg, Ashkan Abbey, Elmira Abdulaeva, Santiago Abengoechea, Prema Abraham, Thomas Ach, Serrhel Adams, Alfredo Adan Civera, Sean Adrean, Hansjurgen Agostini, Suhail Alam, Arturo Alezzandrini, Virgil Alfaro, Daniel Aliseda, Arghavan Almony, Pedro Amat, Payam Amini, Andrew Antoszyk, Luis Arias, Riaz Asaria, Marcos Avila, Carl C Awh, Joaquin Bafalluy, Carl Baker, Francesco Bandello, Mark Barakat, Karen Barraza, Gyorgy Bator, Caroline Baumal, Rubens Belfort Jr, Chris Bergstrom, George Bertolucci, Thomas Bochow, Matthias Bolz, Emilia Borcz, Arnaldo Bordon, David Boyer, Galina Bratko, Michael Brent, Jamin Brown, David M Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Ben Burton, Miguel Busquets, Francisco Cabrera, Carlo Cagini, Jorge Calzada, Peter Campochiaro, John Carlson, Alessandro Castellarin, Carlos Cava, Voraporn Chaikitmongkol, Clement Chan, Emmanuel Chang, Jonathan Chang, Andrew Chang, Steve Charles, Nauman Chaudhry, Caroline Chee, Judy Chen, Fred Chen, Shih-Jen Chen, Richard Cheong-Leen, Allen Chiang, Mark Chittum, David Chow, Brian Connolly, Pierre Loic Cornut, Karl Csaky, Carl Danzig, Arup Das, Vesselin Daskalov, Carmen Desco, Amr Dessouki, John Dickinson, Brian Do, Michael Dollin, Pravin Dugel, Jaroslava Dusova, David Eichenbaum, Bora Eldem, Robert Engstrom, Jan Ernest, Joan Josep Escobar, Simona Esposti, Nicole Eter, Naomi Falk, Andrej Farkas, Leonard Feiner, Nicolas Feltgen, Carlos Fernandez, Alvaro Fernandez Vega, Philip Ferrone, Joao Figueira, Marta Figueroa, Oliver Findl, Howard Fine, Jorge Fortun, Gregory M Fox, Scott Foxman, Carsten Framme, Samantha Fraser-Bell, Arthur Fu, Akira Fukutomi, Nicholas Fung, Federico Furno Sola, Roberto Gallego-Pinazo, Renata Garcia, Alfredo Garcia-Layana, Maciej Gawecki, Sheen George, Faruque Ghanchi, Ghassan Ghorayeb, Roger Goldberg, Michaella Goldstein, Nuno Gomes, Francisco Gomez Ulla, Victor Gonzalez, Craig Greven, Sunil Gupta, Miguel Guzman, Martin Harris, Katja Hatz, Vivienne Hau, Vincent Hau, Ken Hayashi, Jeffrey Heier, Ewa Herba, Vrinda Hershberger, Patrick Higgins, Akito Hirakata, Allen Ho, Nancy Holekamp, Shigeru Honda, Jason Hsu, Allen Hu, Maria Hurcikova, Yasuhiro Ikeda, Ricky Isernhagen, Yasuki Ito, Tim Jackson, Rachael Jacoby, Afsar Jafree, Golnaz Javey, Cameron Javid, Chirag Jhaveri, Mark Johnson, Marek Kacerík, Jakub Kaluzny, Daniel Kampik, Se Woong Kang, Kapil Kapoor, Levent Karabas, Tsutomu Kawasaki, Agnes Kerenyi, Arshad Khanani, Rahul Khurana, Brian Kim, Kazuhiro Kimura, Genichiro Kishino, Shigehiko Kitano, Kendra Klein-Mascia, Gregg Kokame, Jean Francois Korobelnik, Alexey Kulikov, Ajay Kuriyan, Henry Kwong, Robert Kwun, Timothy Lai, Chi-Chun Lai, Philip Laird, Laurent Lalonde, Paolo Lanzetta, Michael Larsen, Caroline Laugesen, Daniel Lavinsky, Olivier Lebreton, Seong Lee, Jaime Levy, Blandina Lipkova, Mimi Liu, Judy Liu, Chris P Lohmann, Nikolas London, Katrin Lorenz, Andrew Lotery, David Lozano Rechy, Silvio Lujan, Patrick Ma, Takatoshi Maeno, Sajjad Mahmood, Fuad Makkouk, Khurram Malik, Dennis Marcus, Alan Margherio, Leonardo Mastropasqua, Raj Maturi, Frank McCabe, Martin McKibbin, Hemal Mehta, Geeta Menon, Jale Mentes, Katarzyna Michalska-Malecka, Aneta Misheva, Yoshinori Mitamura, Paul Mitchell, Yasha Modi, Quresh Mohamed, Javier Montero, Jeffrey Moore, Virgilio Morales Canton, Haia Morori-Katz, Tatiana Morugova, Tomoaki Murakami, Maria Muzyka-Wozniak, Marco Nardi, Jan Nemcansky, Kamila Nester-Ostrowska, Julio Neto, Charles Newell, Massimo Nicolo, Jared Nielsen, Kousuke Noda, Akira Obana, Nahoko Ogata, Hideyasu Oh, Kean Oh, Matthew Ohr, Piotr Oleksy, Scott Oliver, Sebastien Olivier, James Osher, Sehnaz Ozcalişkan, Banu Ozturk, Andras Papp, Kyu Hyung Park, D Wilkin Parke, Maria Cristina Parravano, Sugat Patel, Sunil Patel, Ian Pearce, Joel Pearlman, Fernando Penha, Irfan Perente, Stephen Perkins, Grazia Pertile, Iva Petkova, Tunde Peto, Dante Pieramici, Andreas Pollreisz, Pear Pongsachareonnont, Nadezhda Pozdeyeva, Siegfried Priglinger, Jawad Qureshi, Dorota Raczynska, Rajesh Rajagopalan, Juan Ramirez Estudillo, Paul Raskauskas, Rajiv Rathod, Hessam Razavi, Carl Regillo, Federico Ricci, Soraya Rofagha, Dominika Romanczak, Bożena Romanowska-Dixon, Daniel Rosberger, Irit Rosenblatt, Brett Rosenblatt, Adam Ross, Paisan Ruamviboonsuk, Jose Maria Ruiz Moreno, Gustavo Salomão, Sukhpal Sandhu, Dirk Sandner, Laura Sararols, Osamu Sawada, Ramin Schadlu, Patricio Schlottmann, Claudia Schuart, Berthold Seitz, András Seres, Figen Sermet, Sandeep Shah, Ankur Shah, Rohan Shah, Sumit Sharma, Thomas Sheidow, Veeral Sheth, Akito Shimouchi, Masahiko Shimura, Bartosz Sikorski, Rufino Silva, Michael Singer, Lawrence Singerman, Rishi Singh, Eric Souied, David J Spinak, Georg Spital, Nathan Steinle, Jeffrey Stern, Glenn Stoller, Robert Stoltz, Cameron Stone, Amy Stone, Eric Suan, Masahiko Sugimoto, Iichiro Sugita, Jennifer Sun, Xiaodong Sun, Ivan Suner, Lajos Szalczer, Timea Szecsko, Ali Tabassian, Hitoshi Takagi, Kei Takayama, Alexandre Taleb, James Talks, Gavin Tan, Teruyo Tanabe, Stanford Taylor, Allen Thach, John Thompson, Paul Tlucek, Robert Torti, Daniela Tosheva Guneva, Edit Toth-Molnar, Eduardo Uchiyama, Attila Vajas, Deepali Varma, Balazs Varsanyi, Petja Vassileva, Sara Vaz-Pereira, Miroslav Veith, Jose Ignacio Vela, Francesco Viola, Gianni Virgili, Gábor Vogt, Henrik Vorum, Pamela Weber, Thoalf Wecke, Raymond Wee, Martin Weger, Paul Weishaar, Sanjeewa Wickremasinghe, Thomas Reginald Williams, Thomas Williams, Geoff Williams, Armin Wolf, Jeremy Wolfe, James Wong, David Wong, Ian Wong, Robert Wong, Bogumil Wowra, Edward Wylęgała, Chang-Hao Yang, Tsutomu Yasukawa, Paul Yates, Gursel Yilmaz, Glenn Yiu, Young Hee Yoon, Barak Yoreh, Shigeo Yoshida, Hyeong Gon Yu, Seung Young Yu, Tatiana Yurieva, Leandro Zacharias, Karolina Zaczek Zakrzewska, Alberto Zambrano, Barbara Zatorska, Carlos Zeolite, and Jeffrey Zheutlin

Subjects
Male, Vascular Endothelial Growth Factor A, Diabetic Retinopathy, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, General Medicine, Middle Aged, Drug Administration Schedule, Angiopoietin-2, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Double-Blind Method, Antibodies, Bispecific, Intravitreal Injections, Edema, Humans, Female, Macula Lutea, Aged
Abstract

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Published
2022
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34. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

Author

Jeffrey S Heier, Arshad M Khanani, Carlos Quezada Ruiz, Karen Basu, Philip J Ferrone, Christopher Brittain, Marta S Figueroa, Hugh Lin, Frank G Holz, Vaibhavi Patel, Timothy Y Y Lai, David Silverman, Carl Regillo, Balakumar Swaminathan, Francesco Viola, Chui Ming Gemmy Cheung, Tien Y Wong, Ashkan Abbey, Elmira Abdulaeva, Prema Abraham, Alfredo Adan Civera, Hansjurgen Agostini, Arturo Alezzandrini, Virgil Alfaro, Arghavan Almony, Lebriz Altay, Payam Amini, Andrew Antoszyk, Etelka Aradi, Luis Arias, Jennifer Arnold, Riaz Asaria, Sergei Astakhov, Yury Astakhov, Carl C. Awh, Chandra Balaratnasingam, Sanjiv Banerjee, Caroline Baumal, Matthias Becker, Rubens Belfort, Galina Bratko, William Jr. Z Bridges, Jamin Brown, David M. Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Iksoo Byon, Carlo Cagini, Jorge Calzada, Stone Cameron, Peter Campochiaro, John Carlson, Angela Carneiro, Clement Chan, Emmanuel Chang, Andrew Chang, Daniel Chao, Nauman Chaudhry, Caroline Chee, Andrew Cheek, Shih-Jen Chen, San-Ni Chen, Gemmy Cheung, Saradha Chexal, Mark Chittum, David Chow, Abosede Cole, Brian Connolly, Pierre Loic Cornut, Stephen Couvillion, Carl Danzig, Vesselin Daskalov, Amr Dessouki, Francois Devin, Michael Dollin, Rosa Dolz, Louise Downey, Richard Dreyer, Pravin Dugel, David Eichenbaum, Bora Eldem, Robert Engstrom, Joan Josep Escobar, Nicole Eter, David W. Faber, Naomi Falk, Leonard Feiner, Alvaro Fernandez Vega, Philip Ferrone, Marta Figueroa, Howard Fine, Mitchell Fineman, Gregory M. Fox, Catherine Francais, Pablo Franco, Samantha Fraser-Bell, Nicholas Fung, Federico Furno Sola, Richard Gale, Alfredo Garcia-Layana, Julie Gasperini, Maciej Gawecki, Faruque Ghanchi, Manjot Gill, Michel Giunta, David Glaser, Michaella Goldstein, Francisco Gomez Ulla, Fumi Gomi, Victor Gonzalez, Jordan Graff, Sunil Gupta, Rainer Guthoff, Robyn Guymer, Anton Haas, Robert Hampton, Katja Hatz, Ken Hayashi, Jeffrey Heier, Ewa Herba, Vrinda Hershberger, Patrick Higgins, Nancy Holekamp, Shigeru Honda, James Howard, Allen Hu, Stephen Huddleston, Tomohiro Iida, Hiroko Imaizumi, Yasuo Ito, Yasuki Ito, Sujit Itty, Golnaz Javey, Cameron Javid, Tatsushi Kaga, Jakub Kaluzny, Se Woong Kang, Kapil Kapoor, Levent Karabas, Tsutomu Kawasaki, Patrick Kelty, Agnes Kerenyi, Arshad Khanani, Ramin Khoramnia, Rahul Khurana, Kazuhiro Kimura, Kendra Klein-Mascia, Namie Kobayashi, Laurent Kodjikian, Hideki Koizumi, Gregg Kokame, Alexey Kulikov, Henry Kwong, Robert Kwun, Timothy Lai, Chi-Chun Lai, Laurent Lalonde, Paolo Lanzetta, Michael Larsen, Adrian Lavina, Won Ki Lee, ji Eun Lee, Seong Lee, Jaime Levy, Lucas Lindsell, Mimi Liu, Nikolas London, Andrew Lotery, David Lozano Rechy, Alan Luckie, David Maberley, Takatoshi Maeno, Sajjad Mahmood, Fuad Makkouk, Dennis Marcus, Alan Margherio, Helene Masse, Hisashi Matsubara, Raj Maturi, Sonia Mehta, Geeta Menon, Jale Mentes, Mark Michels, Yoshinori Mitamura, Paul Mitchell, Quresh Mohamed, Jordi Mones, Rodrigo Montemayor Lobo, Javier Montero, Jeffrey Moore, Ryusaburo Mori, Haia Morori-Katz, Raj Mukherjee, Toshinori Murata, Maria Muzyka-Wozniak, Marco Nardi, Niro Narendran, Massimo Nicolo, Jared Nielsen, Tetsuya Nishimura, Kousuke Noda, Anna Nowinska, Hideyasu Oh, Matthew Ohr, Annabelle Okada, Piotr Oleksy, Shinji Ono, Sengul Ozdek, Banu Ozturk, Luis Pablo, Kyu Hyung Park, D. Wilki Parke, Maria Cristina Parravano, Praveen Patel, Apurva Patel, Sunil Patel, Sugat Patel, Daniel Pauleikhoff, Ian Pearce, Joel Pearlman, Iva Petkova, Dante Pieramici, Nadezhda Pozdeyeva, Jawad Qureshi, Dorota Raczynska, Juan Ramirez Estudillo, Rajiv Rathod, Hessam Razavi, Gayatri Reilly, Federico Ricci, Ryan Rich, Bożena Romanowska-Dixon, Irit Rosenblatt, Jose Maria Ruiz Moreno, Stefan Sacu, Habiba Saedon, Usman Saeed, Min Sagong, Taiji Sakamoto, Sukhpal Sandhu, Laura Sararols, Mario Saravia, Ramin Schadlu, Patricio Schlottmann, Tetsuju Sekiryu, András Seres, Figen Sermet, Sumit Shah, Rohan Shah, Ankur Shah, Thomas Sheidow, Veeral Sheth, Chieko Shiragami, Bartosz Sikorski, Rufino Silva, Lawrence Singerman, Robert Sisk, Torben L. Sørensen, Eric Souied, David-J Spinak, Giovanni Staurenghi, Robert Steinmetz, Glenn Stoller, Robert Stoltz, Eric Suan, Ivan Suner, Yzer Suzanne, Ramin Tadayoni, Kanji Takahashi, Kei Takayama, Alexandre Taleb, James Talks, Hiroko Terasaki, John Thompson, Edit Toth-Molnar, Khoi Tran, Raman Tuli, Eduardo Uchiyama, Attila Vajas, Janneke Van Lith-Verhoeven, Balazs Varsanyi, Gianni Virgili, Gábor Vogt, Michael Völker, David Warrow, Pamela Weber, John A. Wells, Sanjeewa Wickremasinghe, Mark Wieland, Geoff Williams, Thomas Williams, David Wong, King Wong, James Wong, Ian Wong, Robert Wong, Bogumil Wowra, Charles C. Wykoff, Ayana Yamashita, Kanako Yasuda, Gursel Yilmaz, Glenn Yiu, Ai Yoneda, Young Hee Yoon, Barak Yoreh, HyeongGon Yu, Seung Young Yu, Tatiana Yurieva, Alberto Zambrano, Barbara Zatorska, and Carlos Zeolite

Subjects
Aged, 80 and over, Male, Vascular Endothelial Growth Factor A, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, General Medicine, Drug Administration Schedule, Angiopoietin-2, Macular Degeneration, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Double-Blind Method, Antibodies, Bispecific, Intravitreal Injections, Humans, Female, Aged
Abstract

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Published
2022
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35. Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise

Author

Madoka KOHNO, Anayt ULLA, Rina TANIGUCHI, Akane OHISHI, Kako HIRAYAMA, Yuma TAKEMURA, Shoichiro TAKAO, Yuki KANAZAWA, Yuki MATSUMOTO, Masafumi HARADA, Tomoya FUKAWA, Hiro-omi KANAYAMA, Takayuki UCHIDA, Toshio SUZUKI, and Takeshi NIKAWA

Subjects
Male, Mice, Nutrition and Dietetics, Case-Control Studies, Dietary Supplements, Medicine (miscellaneous), Animals, Soybeans, Muscle Strength, Dietary Proteins, Muscle, Skeletal
Abstract

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

Published
2023

36. A psychological intervention for caries active young adults, a randomized controlled trial

Author

Jennie Hagman, Ulla Wide, Helene Werner, and Magnus Hakeberg

Subjects
Male, medicine.medical_specialty, Dental Caries Susceptibility, Dental Plaque, Psychological intervention, Dental Caries, Oral health, Psychosocial Intervention, Acceptance and commitment therapy, law.invention, Young Adult, Gingivitis, Randomized controlled trial, law, Intervention (counseling), Internal medicine, Humans, Medicine, Young adult, General Dentistry, business.industry, Consolidated Standards of Reporting Trials, Female, medicine.symptom, business
Abstract

OBJECTIVE The aim of the present study was to evaluate the effect of a brief version of the behavioral intervention Acceptance and Commitment Therapy (ACT) on reducing gingivitis and plaque levels after 18 weeks. MATERIALS AND METHODS One hundred thirty-five caries-active young adults (18-25 years of age), recruited from two public dental clinics, participated in this parallel group randomized control trial (RCT). Participants in the intervention (n = 67) received two ACT sessions in combination with standard information on oral health, and participants allocated to the control group (n = 68) received standard information only. Gingivitis and plaque levels were recorded at baseline and at the 9- and 18-week follow-ups. The effect of the intervention versus standard information alone was analyzed by intention-to-treat and per protocol, applying the General Linear Model (GLM). Exploratory analyses for the intervention and control groups were conducted to evaluate the effect of gender and smoking habits on the gingivitis and plaque outcome. The CONSORT guidelines for RCT were followed. RESULTS A significant decrease in gingivitis and plaque levels was observed over time, irrespective of treatment allocation. However, the ACT intervention was not significantly more effective at reducing gingivitis and plaque scores than standard information alone, even though the intervention participants had maintained their improvement to a greater extent. The exploratory analysis revealed that females improved their gingivitis and plaque levels significantly more than the males in the intervention group (p = 0.025 for gingivitis and p = 0.013 for plaque). CONCLUSION A brief ACT intervention was not proven to be more effective than standard information alone at improving oral health in a sample of young adults with poor oral health. However, ACT seems to have a positive effect on oral health among females. (TRN ISRCTN15009620).

Published
2021
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37. Hospital Presentation for Self-Harm in Youth as a Risk Marker for Later Psychotic and Bipolar Disorders

Author

David Gyllenberg, Mika Gissler, Ulla Lång, Ian Kelleher, Juha Veijola, Koen Bolhuis, Antti Kääriälä, Child and Adolescent Psychiatry / Psychology, Nuorisopsykiatria, University of Helsinki, and HUS Psychiatry

Subjects
Adult, Male, Psychosis, medicine.medical_specialty, Bipolar Disorder, Adolescent, AcademicSubjects/MED00810, 3124 Neurology and psychiatry, Young Adult, 03 medical and health sciences, mania, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Risk Factors, medicine, Humans, Longitudinal Studies, Registries, bidirectional, Bipolar disorder, Psychiatry, Finland, mania/epidemiology, suicide, register, Proportional hazards model, business.industry, Hazard ratio, medicine.disease, Mental illness, 030227 psychiatry, 3. Good health, schizophrenia, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Cohort, Female, epidemiology, Emergency Service, Hospital, business, Self-Injurious Behavior, 030217 neurology & neurosurgery, Regular Articles, Cohort study
Abstract

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.

Published
2021
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38. Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors: A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

Author

Leontien C. M. Kremer, Eugene Suh, Bradley Benson, Gregory J. Aune, Monica Muraca, Edit Bardi, Daniel A. Mulrooney, Roderick Skinner, Gill Levitt, Liane Lockwood, Chris Plummer, Renée L. Mulder, Louis S. Constine, W. Hamish B. Wallace, Eva Frey, Christina Schindera, Ming H. Chen, Melissa M. Hudson, Emily S. Tonorezos, Elvira C. van Dalen, Ulrike Hennewig, Helena J H van der Pal, Jutta Bergler-Klein, Ulla Martinsson, Katrin Scheinemann, and Matthew J. Ehrhardt

Subjects
Adult, Diagnostic Screening Programs, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Time Factors, Adolescent, medicine.medical_treatment, Antineoplastic Agents, Coronary Artery Disease, Risk Assessment, Coronary artery disease, Young Adult, Cancer Survivors, Predictive Value of Tests, Risk Factors, Neoplasms, Prevalence, medicine, Humans, Age of Onset, Family history, Young adult, Child, Radiation Injuries, 610 Medicine & health, Radiotherapy, business.industry, Incidence, Clinical study design, Cancer, Guideline, Middle Aged, Prognosis, medicine.disease, Cardiotoxicity, Radiation therapy, Systematic review, Oncology, Child, Preschool, Female, business, 360 Social problems & social services
Abstract

Background Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. Aim To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. Methods A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. Results 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses ≥15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. Conclusion These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.

Published
2021
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39. Self-Reported Medication Use and Urinary Drug Metabolites in the German Chronic Kidney Disease (GCKD) Study

Author

Robert P. Mohney, Peter J. Oefner, Peggy Sekula, Kai-Uwe Eckardt, Gckd Study Investigators, Anna Köttgen, Johanna Mielke, Matthias Wuttke, Fruzsina Kotsis, Edward D. Karoly, Michael S. Becker, Pascal Schlosser, and Ulla T. Schultheiss

Subjects
Male, Drug, medicine.medical_specialty, Urinary system, media_common.quotation_subject, Metabolite, Urine, Sensitivity and Specificity, Mass Spectrometry, Medication Adherence, Cohort Studies, chemistry.chemical_compound, Germany, Internal medicine, medicine, Humans, Clinical Epidemiology, Renal Insufficiency, Chronic, Medical prescription, Aged, media_common, business.industry, General Medicine, Middle Aged, Ibuprofen, medicine.disease, Acetaminophen, Pharmaceutical Preparations, chemistry, Nephrology, Polypharmacy, Female, Self Report, business, medicine.drug, Kidney disease
Abstract

Background Polypharamacy is common among patients with chronic kidney disease (CKD), but little is known about urinary excretion of many drugs and their metabolites among CKD patients. Methods To evaluate self-reported medication use in relation to urine drug metabolite levels in a large cohort of CKD patients, the Germany Chronic Kidney Disease study, we ascertained self-reported use of 158 substances and 41 medication groups and coded active ingredients according to the Anatomical Therapeutic Chemical classification system. We used a nontargeted mass spectrometry-based approach to quantify metabolites in urine; calculated specificity, sensitivity, and accuracy of medication use and corresponding metabolite measurements; and used multivariable regression models to evaluate associations and prescription patterns. Results Among 4885 participants, there were 108 medication-drug metabolite pairs based on reported medication use and 78 drug metabolites. Accuracy was excellent for measurements of 36 individual substances in which the unchanged drug was measured in urine (median, 98.5%; range 61.1%-100%). For 66 pairs of substances and their related drug metabolites, median measurement-based specificity and sensitivity were 99.2% (range 84.0%-100%) and 71.7% (range 1.2%-100%), respectively. Commonly prescribed medications for hypertension and cardiovascular risk reduction-including angiotensin-II receptor blockers, calcium channel blockers, and metoprolol-showed high sensitivity and specificity. Although self-reported use of prescribed analgesics (acetaminophen, ibuprofen) was

Published
2021
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40. Effect of Topical Antibiotics on Duration of Acute Infective Conjunctivitis in Children: A Randomized Clinical Trial and a Systematic Review and Meta-analysis

Author

Minna Honkila, Ulla Koskela, Tero Kontiokari, Marja-Leena Mattila, Aila Kristo, Raija Valtonen, Suvi Sarlin, Niko Paalanne, Irma Ikäheimo, Tytti Pokka, Matti Uhari, Marjo Renko, and Terhi Tapiainen

Subjects
Male, Child, Preschool, Acute Disease, Moxifloxacin, Humans, Female, General Medicine, Ophthalmic Solutions, Child, Conjunctivitis, Anti-Bacterial Agents, Randomized Controlled Trials as Topic
Abstract

ImportanceAlthough topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain.ObjectiveTo assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis.Design, Setting, and ParticipantsA randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis.InterventionsParticipants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention.Main Outcomes and MeasuresThe primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6.ResultsThe randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, −1.9 days; 95% CI, −3.7 to −0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of children who had symptoms of conjunctivitis on days 3 to 6 compared with placebo eye drops (odds ratio, 0.59; 95% CI, 0.39 to 0.91).Conclusions and RelevanceIn this randomized clinical trial and systematic review and meta-analysis, topical antibiotics were associated with significantly shorter durations of conjunctival symptoms in children with acute infective conjunctivitis.Trial RegistrationClinicalTrialsRegister.eu Identifier: 2013-005623-16

Published
2022

41. Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites

Author

Niemelä, O. (Onni), Halkola, A. S. (Anni S.), Bloigu, A. (Aini), Bloigu, R. (Risto), Nivukoski, U. (Ulla), Pohjasniemi, H. (Heidi), Kultti, J. (Johanna), Tampere University, Clinical Medicine, and Seinäjoen keskussairaala VA

Subjects
Male, Adult, Erythrocyte Indices, Alcohol Drinking, autoantibodies, Acetaldehyde, calprotectin, Hemolysis, Catalysis, Receptors, Urokinase Plasminogen Activator, Inorganic Chemistry, oxidative stress, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Inflammation, Blood Cells, Haptoglobins, Ethanol, Organic Chemistry, Immunity, Transferrin, neutrophil, Bilirubin, General Medicine, Middle Aged, haptoglobin, Computer Science Applications, Alcoholism, erythrocyte, ethanol, hemolysis, leukocyte, Female, 3111 Biomedicine, Leukocyte L1 Antigen Complex, Biomarkers, Acute-Phase Proteins
Abstract

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

Published
2022

42. Progression or Not – A Small Natural History Study of Genetical Confirmed Congenital Myopathies

Author

Ulla Werlauff, Nanna Witting, Pernille Diemer Hansen, and John Vissing

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Muscle Proteins, Gene mutation, Cohort Studies, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Internal medicine, Genotype, medicine, Humans, Respiratory function, 030212 general & internal medicine, business.industry, Middle Aged, medicine.disease, Congenital myopathy, Natural history, DNM2, Phenotype, Neurology, Mutation, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Natural history study, Follow-Up Studies, Myopathies, Structural, Congenital
Abstract

Background: Clinical characteristics of patients with congenital myopathies (CM) are well known but there is a lack of knowledge about the natural history and course of disease of the different genetic subtypes. In 2010 we assessed the national cohort of Danish patients with CM to decide genetic diagnosing and describe genotype- phenotype relationships. AIM of this follow-up study was to evaluate the course of disease since the initial study and to evaluate the applicability of standard assessment methods to reflect change over time and patients own opinion on the course of disease. Methods: All available genetically diagnosed patients studied by us in 2010 (n = 41) were invited to the follow-up study; assessment of motor function (MFM-32), muscle strength (MRC %)and respiratory function (FVC %) and prime assessor were the same as in the initial study. Patients were asked whether the course of disease had progresses, was stable or had improved. Results: 23 patients (15–61 y) accepted the invitation. Mean follow-up time was 7.7 years. Loss of muscle strength was more prominent in patients with mutations in DNM2, RYR1 and TPM2/3 genes and deterioration in FVC % was more evident in patients carrying NEB and ACTA1 gene mutations. MFM-sum score was less sensitive to change compared to MRC-sum score. In general, agreement between the patient’s own opinion of the course of disease and results of assessments was good. Conclusion: The number of patients in the study is too small to be conclusive, but the results indicate that CM can be stable or slowly progressive depending on the genetic subtype.

Published
2021
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43. High incidence of inguinal hernias among patients with congenital abdominal wall defects: a population-based case–control study

Author

Mika Gissler, Ulla Sankilampi, Anna Hyvärinen, Ilkka Helenius, Asta Tauriainen, Johanna Syvänen, Nelly Kalliokoski, Samuli Harju, Arimatias Raitio, Department of Surgery, HUS Musculoskeletal and Plastic Surgery, University of Helsinki, I kirurgian klinikka (Töölö), Tampere University, Clinical Medicine, and Tays Research Services

Subjects
Male, BOYS, Pediatrics, medicine.medical_specialty, Population, INFANTS, Hernia, Inguinal, CHILDREN, Exomphalos, Abdominal wall, 03 medical and health sciences, 0302 clinical medicine, 3123 Gynaecology and paediatrics, 030225 pediatrics, medicine, Humans, QUALITY, Hernia, RATES, Child, education, Finland, Gastroschisis, SHUNTS, education.field_of_study, Omphalocele, business.industry, Incidence, Incidence (epidemiology), Abdominal Wall, Inguinal hernia, Infant, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, 3. Good health, medicine.anatomical_structure, Case-Control Studies, 030220 oncology & carcinogenesis, Relative risk, CLOSURE, Pediatrics, Perinatology and Child Health, RISK-FACTORS, Original Article, Female, business, Hernia, Umbilical
Abstract

The aim of this nationwide population-based case–control study was to assess the incidence of inguinal hernia (IH) among patients with congenital abdominal wall defects. All infants born with congenital abdominal wall defects between Jan 1, 1998, and Dec 31, 2014, were identified in the Finnish Register of Congenital Malformations. Six controls matched for gestational age, sex, and year of birth were selected for each case in the Medical Birth Register. The Finnish Hospital Discharge Register was searched for relevant diagnosis codes for IH, and hernia incidence was compared between cases and controls. We identified 178 infants with gastroschisis and 150 with omphalocele and selected randomly 1968 matched, healthy controls for comparison. Incidence of IH was significantly higher in gastroschisis girls than in matched controls, relative risk (RR) 7.20 (95% confidence interval [CI] 2.25–23.07). In boys with gastroschisis, no statistically significant difference was observed, RR 1.60 (95% CI 0.75–3.38). Omphalocele was associated with higher risk of IH compared to matched controls, RR 6.46 (95% CI 3.90–10.71), and the risk was equally elevated in male and female patients.Conclusion: Risk of IH is significantly higher among patients with congenital abdominal wall defects than in healthy controls supporting hypothesis that elevated intra-abdominal pressure could prevent natural closure of processus vaginalis. Parents should be informed of this elevated hernia risk to avoid delays in seeking care. We also recommend careful follow-up during the first months of life as most of these hernias are diagnosed early in life.What is Known:• Inguinal hernia is one of the most common disorders encountered by a pediatric surgeon.• Prematurity increases the risk of inguinal hernia.What is New:• Children with congenital abdominal wall defects have a significantly higher risk of inguinal hernia than general population.• Families should be informed of this elevated hernia risk to avoid delays in seeking care.

Published
2021
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44. Association of Metformin, Other Antidiabetic Medications, and Statins With Incidence of Colon Cancer in Patients With Type 2 Diabetes

Author

Peeter Karihtala, Martti Arffman, Ulla Puistola, Mikko Marttila, Esa Läärä, Arja Jukkola, Elina Urpilainen, Sami Erkinantti, Ari Hautakoski, and Reijo Sund

Subjects
Adult, Male, medicine.medical_specialty, Epidemiology, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Aged, Retrospective Studies, business.industry, Incidence, Hazard ratio, Cohort, Gastroenterology, Retrospective cohort study, Middle Aged, medicine.disease, Colorectal cancer, Metformin, Nested case–control, Diabetes Mellitus, Type 2, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Colonic Neoplasms, Nested case-control study, 030211 gastroenterology & hepatology, business, medicine.drug, Cohort study
Abstract

Background Metformin and statins may have anticancer effects, with plausible cellular mechanisms. However, the association of these agents with the risk of colorectal cancer is unclear. Patients and Methods This was a retrospective cohort study on a large population (N = 316,317) of patients with type 2 diabetes. Data were obtained from the Diabetes in Finland database (FinDM). In a full cohort analysis, hazard ratios (HRs) with their 95% confidence intervals (CIs) for ever use versus never use were estimated using a multiple Poisson regression model. A nested case–control design within the cohort was used to examine the association of colon cancer (CC) with the defined daily dose of medication. The data were analyzed by conditional logistic regression. The analyses were adjusted for the patient’s age, sex, and duration of diabetes. Results In total, 1351 CC cases were diagnosed during 1996-2011. The results revealed insufficient evidence for an association between metformin (HR, 1.01; 95% CI, 0.90-1.14), other oral antidiabetic medications (HR, 1.05; 95% CI, 0.93-1.19), insulin (HR, 1.02; 95% CI, 0.86-1.22), or statins (HR, 0.94; 95% CI, 0.84-1.05) and the incidence of CC in the full cohort analysis. The results from the case–control study were similar, with no consistent trend in the incidence of CC according to the cumulative dose of metformin or the other studied medications. Conclusion This study found insufficient evidence for an association between metformin, insulin, other oral type 2 diabetes medications, or statins and the incidence of CC.

Published
2021
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45. β-Lactoglobulin Is Insulinotropic Compared with Casein and Whey Protein Ingestion during Catabolic Conditions in Men in a Double-Blinded Randomized Crossover Trial

Author

Britt Christensen, Bolette Hartmann, Niels Møller, Elin Rakvaag, Maike Mose, Jens Otto Lunde Jørgensen, Niels Jessen, Ulla Ramer Mikkelsen, Nikolaj Rittig, and Jens J. Holst

Subjects
Adult, Male, medicine.medical_specialty, Whey protein, fasting, Phenylalanine, medicine.medical_treatment, Muscle Proteins, Medicine (miscellaneous), Gastric Inhibitory Polypeptide, Lactoglobulins, Young Adult, Gastric inhibitory polypeptide, Double-Blind Method, Casein, Internal medicine, medicine, Humans, Ingestion, skeletal muscle, dairy protein, Cross-Over Studies, Nutrition and Dietetics, endotoxemia, business.industry, Insulin, Caseins, Skeletal muscle, Crossover study, Whey Proteins, Endocrinology, medicine.anatomical_structure, immobilization, Bolus (digestion), business
Abstract

BACKGROUND: Muscle loss during acute infectious disease is mainly triggered by inflammation, immobilization, and malnutrition.OBJECTIVE: The objective was to compare muscle protein kinetics and metabolism following ingestion of the dairy protein supplements β-lactoglobulin (BLG), casein (CAS), and whey (WHE) during controlled catabolic conditions.METHODS: We used a randomized crossover design (registered at clinicaltrials.gov as NCT03319550) to investigate 9 healthy male participants [age: 20-40 y; BMI (in kg/m2) 20-30] who were randomly assigned servings of BLG, CAS, or WHE (0.6 g protein/kg, one-third as bolus and two-thirds as sip every 20 min) on 3 separate occasions separated by ∼6-8 wk. The participants received an infusion of lipopolysaccharide (1 ng/kg) combined with 36 h of fasting and bed rest before each study day, mimicking a clinical catabolic condition. The forearm model and isotopic tracer techniques were used to quantify muscle protein kinetics. Muscle biopsy specimens were obtained and intramyocellular signaling investigated using Western blot.RESULTS: BLG, CAS, and WHE improved the net balance of phenylalanine (NBphe) from baseline with ∼75% (P < 0.001) with no difference between interventions (primary outcome, P < 0.05). No difference in rates of appearance and disappearance of phenylalanine or in intramyocellular signaling activation was found between interventions (secondary outcomes). The incremental AUC for serum insulin was 62% higher following BLG compared with CAS (P < 0.001) and 30% higher compared with WHE (P = 0.002), as well as 25% higher in WHE compared with CAS (P = 0.006). Following BLG consumption, plasma concentrations of glucose-dependent insulinotropic peptide (GIP) increased 70% compared with CAS (P = 0.001) and increased 34% compared with WHE (P = 0.06). No significant difference was found between WHE and CAS (P = 0.12).CONCLUSION: BLG, WHE, and CAS have similar effects on muscle in young male participants during catabolic conditions. BLG showed specific, possibly GIP-dependent, insulinotropic properties, which may have future clinical implications.

Published
2021
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46. Prolonged lipopolysaccharide-induced illness elevates glucagon-like peptide-1 and suppresses peptide YY: A human-randomized cross-over trial

Author

Katrine Brodersen, Maike Mose, Ulla Ramer Mikkelsen, Jens Otto Lunde Jørgensen, Michael Festersen Nielsen, Niels Møller, Anne‐Marie Wegeberg, Christina Brock, Bolette Hartmann, Jens Juul Holst, and Nikolaj Rittig

Subjects
Inflammation, Lipopolysaccharides, Male, Cross-Over Studies, endotoxemia, Physiology, Nausea, wireless motility capsule, Nausea/chemically induced, Gastrointestinal Hormones, Glucagon-Like Peptide 1, Physiology (medical), gastrointestinal transit times, Humans, Peptide YY, Gastrointestinal Motility
Abstract

Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality rate. There is a lack of human controlled studies exploring gastric emptying rates and underlying mechanisms during inflammatory conditions. We aimed to investigate if systemic inflammation in young men delays gastro-intestinal transit times, lowers motility, and affects gastrointestinal hormone secretion. This substudy of a randomized crossover trial investigated eight healthy young men on two separate occasions; (I) following an overnight fast (healthy conditions/HC) and (II) fasting and bedrest combined with two lipopolysaccharide (LPS) injections of 1 ng kg-1 following an overnight fast and 0.5 ng kg-1 following another 24 h (systemic inflammation/SI). A standardized protein beverage and a SmartPill capsule (a wireless gastrointestinal monitoring system) were swallowed during each occasion. Whole gut transit time was comparable between HC and SI. SI decreased gastric mean pressure peak amplitude (p = 0.04) and increased pH rise across the pylorus and small bowel pH (p = 0.02) compared with HC. Glucagon-like peptide-1 was elevated during SI compared with HC (p = 0.04). Peptide YY was lower during SI compared with HC (p = 0.007). Prolonged LPS exposure combined with fasting and bedrest elevated glucagon-like peptide 1 concentrations, which may play a role for the nausea and loss of appetite typically associated with SI.

Published
2022
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47. Characteristics and treatable traits of patients with chronic obstructive pulmonary disease (COPD) with and without paid employment

Author

Marianne de Man, Jeanine Antons, Remco S. Djamin, Martijn A. Spruit, Alex J van 't Hul, Peter Ascanius Jacobsen, Daisy J.A. Janssen, Ulla Møller Weinreich, Pulmonologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Health Services Research, and RS: CAPHRI - R1 - Ageing and Long-Term Care

Subjects
Male, Time Factors, IMPACT, medicine.medical_treatment, Vital Capacity, Psychological intervention, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Quality of life, Risk Factors, QUALITY-OF-LIFE, Forced Expiratory Volume, 030212 general & internal medicine, Lung, Netherlands, COPD, Occupation, Exercise Tolerance, PRODUCTIVITY, Middle Aged, Prognosis, Checklist, PREVALENCE, Phenotype, Workforce, Female, Workforce connection, Employment, medicine.medical_specialty, Referral, Pulmonary disease, Nutritional Status, Walk Test, Risk Assessment, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Diseases of the respiratory system, All institutes and research themes of the Radboud University Medical Center, PEOPLE, Internal medicine, medicine, Humans, Muscle Strength, Aged, WORK, RC705-779, business.industry, Salaries and Fringe Benefits, Research, BIRMINGHAM COPD, SMOKING-CESSATION, medicine.disease, Cross-Sectional Studies, Nutrition Assessment, 030228 respiratory system, Smoking cessation, Sedentary Behavior, business, Chronic Obstructive Pulmonary Disease (COPD)
Abstract

Introduction Patients with COPD are vulnerable to workforce detachment. Better knowledge of features associated with paid work loss might be of help to design and select appropriate interventions. Method This cross-sectional study aimed to explore the presence of treatable traits in COPD patients without paid work. Patients with COPD below 65 years at first referral to a hospital-based patient clinic were included. Using binary logistic regression analysis, the relationship between paid work and the following characteristics was explored: low daily physical activity, exercise, active smoking, Medical Research Council dyspnea scale (MRC), poor nutritional status, exacerbations, and fatigue (checklist individual strength (CIS)). Variables were adjusted for age, sex, forced expiratory volume in 1 s (FEV 1), and education level. Results In total, 191 patients (47.3%) were without paid work. The following treatable traits were related to not being in paid work: Conclusion Patients without paid work are more likely to have treatable traits with 6MWD revealing the most significant association.

Published
2021
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48. Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes

Author

Sari Niinistö, Carin Andrén Aronsson, Nicole Frank, Roy N. Tamura, Anette-G. Ziegler, Randi K. Johnson, Jill M. Norris, Jorma Toppari, Ulla Uusitalo, Suvi M. Virtanen, Marian Rewers, William Hagopian, Jeffrey P. Krischer, Jimin Yang, and Beena Akolkar

Subjects
Adult, Male, 0301 basic medicine, Glutens, Offspring, Pregnancy Trimester, Third, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, The Environmental Determinants of Diabetes in the Young, Autoimmunity, 030209 endocrinology & metabolism, medicine.disease_cause, Diet Surveys, Article, Food group, Eating, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, Environmental health, Internal Medicine, medicine, Humans, Autoantibodies, Type 1 diabetes, Proportional hazards model, business.industry, Insulin, Postpartum Period, Infant, Newborn, Maternal Nutritional Physiological Phenomena, medicine.disease, Diet, Breast Feeding, Diabetes Mellitus, Type 1, 030104 developmental biology, Female, business
Abstract

AIMS/HYPOTHESIS: We aimed to investigate the association between maternal consumption of gluten-containing foods and other selected foods during late pregnancy and offspring risk of islet autoimmunity (IA) and type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: The TEDDY study recruited children at high genetic risk for type 1 diabetes at birth, and prospectively follows them for the development of IA and type 1 diabetes (n=8556). A questionnaire on the mother’s diet in late pregnancy was completed by 3-4 months postpartum. The maternal daily intake was estimated from a food frequency questionnaire for eight food groups: gluten-containing foods, non-gluten cereals, fresh milk, sour milk, cheese products, soy products, lean/medium-fat fish and fatty fish. For each food, we described the distribution of maternal intake among the four participating countries in the TEDDY study and tested the association of tertile of maternal food consumption with risk of IA and type 1 diabetes using forward selection time-to-event Cox regression. RESULTS: By 28 February 2019, 791 cases of IA and 328 cases of type 1 diabetes developed in TEDDY. There was no association between maternal late-pregnancy consumption of gluten-containing foods or any of the other selected foods and risk of IA, type 1 diabetes, insulin autoantibody-first IA or GAD autoantibody-first IA (all p≥0.01). Maternal gluten-containing food consumption in late pregnancy was higher in Sweden (242 g/day), Germany (247 g/day) and Finland (221 g/day) than in the USA (199 g/day) (pairwise p

Published
2021
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49. Safety and oncological outcome following radiofrequency ablation of small renal masses in a single center

Author

Claus Verner Jensen, Ulla Germer, Ann Buhl Bersang, Martin Andreas Røder, Mette Holm, and Karina Sif Søndergaard Mosholt

Subjects
Male, medicine.medical_specialty, Percutaneous, Radiofrequency ablation, Urology, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Single Center, law.invention, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, law, medicine, Humans, Carcinoma, Renal Cell, Retrospective Studies, Radiofrequency Ablation, business.industry, medicine.disease, Kidney Neoplasms, Treatment Outcome, surgical procedures, operative, Nephrology, Catheter Ablation, Female, Radiology, Neoplasm Recurrence, Local, business
Abstract

To evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) for small renal masses (SRMs) at a large single-institution center during a period of 12 years.A total of 118 patients underwent RFA for SRM between July 2006 and July 2018 at our institution. We included demographic information, comorbidity, procedural details, and oncological outcome in the analysis. Survival analysis was performed using competing risk.87 males and 31 females with median age 66 years underwent RFA. Median tumor size was 23 mm. Tumor biopsy was performed in 94% of cases, of which 56% were confirmed renal cell carcinoma (RCCs). Twenty-eight patients had benign tumors or underwent treatment for recurrence of prior RCC. Median follow-up of 5 years. Median Charlson Comorbidity Index was 5. Major complications occurred in 1.7%. No change in kidney function was observed. The initial treatment response was 98%. Among patients treated for newly diagnosed radiological suspected RCC without Von Hippel-Lindau or benign biopsy (90 pts), the cumulative incidence of radiological recurrence after 5 and 10 years was 6.6% (95% CI: 0.8-12%) and 16% (95% CI: 4.2-28%), respectively. Three patients died of RCC during follow-up. The cumulative incidence of kidney cancer death was 4.5% (95% CI: 4.3-13%) after 10 years. The incidence of other-cause mortality was 50% (95% CI: 34-67%).CT-guided RFA is a safe and effective treatment option for patients unsuitable for surgery. RFA is a good alternative to partial or radical nephrectomy for SRMs, although randomized trials comparing surgery to minimally invasive thermal ablation techniques are missing.

Published
2021
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50. Impact of Systemic Corticosteroids on Mortality in Older Adults With Critical COVID-19 Pneumonia

Author

María Teresa Bellver-Álvarez, Virginia Pardo‐Guimera, Juan Torres-Macho, Beatriz Mestre-Gómez, Mirian Akasbi-Montalvo, Esther Piniella-Ruiz, Pablo Ryan-Murua, Sara Vinat-Prado, Nuria Muñoz-Rivas, Ana Bustamante-Fermosel, Mariano Ulla-Anés, A. Franco-Moreno, Rita Cabezas-Olea, Belén Escolano-Fernández, Carmen Santamaría-García, and María Soledad Acedo-Gutiérrez

Subjects
Research Report, Corticosteroid treatment, Male, Aging, medicine.medical_specialty, medicine.drug_class, Critical ill patients, AcademicSubjects/MED00280, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, Humans, Medicine, COVID-19 pneumonia, Hospital Mortality, 030212 general & internal medicine, Adverse effect, Retrospective Studies, Aged, 80 and over, Lung, SARS-CoV-2, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, medicine.disease, Pathophysiology, COVID-19 Drug Treatment, Hospitalization, In-hospital mortality, Pneumonia, medicine.anatomical_structure, Respiratory failure, Older adults, Cohort, AcademicSubjects/SCI00960, Corticosteroid, Female, Geriatrics and Gerontology, Respiratory Insufficiency, business
Abstract

Background The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In severe acute respiratory syndrome coronavirus 2 infection, the host immune response is thought to play a key role in the pathophysiological effects of lung damage. Therefore, corticosteroid therapy could modulate inflammation-mediated pulmonary injury and thereby reduce progression to severe respiratory failure and death. The aim of this study was to analyze the safety and clinical efficacy of corticosteroid therapy in older adults with severe COVID-19 pneumonia. Method We reviewed the clinical records of confirmed COVID-19 patients aged 75 years or older admitted to our hospital over a 3-month period (March 1–May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization guidance on COVID-19, our hospital protocol added corticosteroid for COVID-19 treatment. We compared in-hospital mortality among patients with critical COVID-19 who received corticosteroids therapy and those who did not. Results In total, 88 patients (61.5%) were treated with corticosteroids, and 55 patients (38.4%) were not. Both groups were similar in baseline characteristics. The median age was 85 years (interquartile range: 82–89), and 61.5% (88/143) were male. In-hospital mortality was lower in the corticosteroid group (68.2%) compared with patients in the noncorticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (hazard ratio: 0.61; 95% CI: 0.41–0.93; p = .006). Conclusions In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.

Published
2021
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