The role of population pharmacokinetic-pharmacodynamic modelling in antimalarial chemotherapy

Despite the high rates of mortality and morbidity associated with malaria very few new antimalarial drugs are being developed. Hence there is much to be gained by optimising currently available antimalarials. Using pharmacokinetic and pharmacodynamic data from field trials where mefloquine was administered either alone or in combination with artesunate important information regarding optimal dosing for the clinician has been obtained. The pharmacokinetics of mefloquine were influenced relatively little, or not at all, by factors such as age, sex, or measures of acute malaria severity. Splitting the 25 mglkg dose of mefloquine monotherapy was associated with a 50% increase in oral bioavailability, and bioavailability increased by 20% for the split dose on the combination treatment. Oral bioavailability was also observed to be associated with more rapid parasite clearance, a surrogate outcome measure for cure. A mechanistic mathematical model was developed that describes the change in total parasite burden with time in vivo, in the presence of mefloquine. Estimates for the pharmacokinetic and pharmacodynamic parameters were obtained from population modelling of pharmacokinetic and in vitro pharmacodynamic data, both derived from the same region. Model simulations confirmed that, early in the evolution of resistance, conventional assessments of the therapeutic response 28 days after treatment underestimate considerably the level of resistance. Longer follow-up is required. The model also indicates that initial deployment of a lower (l5-mglkg) dose of mefloquine provides a greater opportunity for the selection of resistant mutants and would be expected to lead more rapidly to resistance than de novo use of the higher (25-mglkg) dose. From the modelling of malaria therapy data it was observed that even in the absence of drugs the patient parasitaemia versus time profiles varied greatly between both patients and parasites. Parasite multiplication rate every 48 hours was estimated to be approximately 8 fold

Relationship between body adiposity measures and risk of primary knee and hip replacement for osteoarthritis: a prospective cohort study

Introduction: Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. It is unknown whether the adipose mass and the distribution of adipose mass are associated with the risk of primary knee and hip replacement for osteoarthritis. The aim of the present investigation was to examine this in a cohort study. Methods: A total of 39,023 healthy volunteers from Melbourne, Australia were recruited for a prospective cohort study during 1990 to 1994. Their body mass index, waist circumference, and waist-to-hip ratio were obtained from direct anthropometric measurements. The fat mass and percentage fat were estimated from bioelectrical impedance analysis. Primary knee and hip replacements for osteoarthritis between 1 January 2001 and 31 December 2005 were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for primary joint replacement associated with each adiposity measure. Results: Comparing the fourth quartile with the first, there was a threefold to fourfold increased risk of primary joint replacement associated with body weight (HR = 3.44, 95% confidence interval (CI) = 2.83 to 4.18), body mass index (HR = 3.44, 95% CI = 2.80 to 4.22), fat mass (HR = 3.51, 95% CI = 2.87 to 4.30), and percentage fat (HR = 2.99, 95% CI = 2.46 to 3.63). The waist circumference (HR = 2.77, 95% CI = 2.26 to 3.39) and waist-to-hip ratio (HR = 1.46, 95% CI = 1.21 to 1.76) were less strongly associated with the risk. Except for the waist-to-hip ratio, which was not significantly associated with hip replacement risk, all adiposity measures were associated with the risk of both knee and hip joint replacement, and were significantly stronger risk factors for knee. Conclusions: Risk of primary knee and hip joint replacement for osteoarthritis relates to both adipose mass and central adiposity. This relationship suggests both biomechanical and metabolic mechanisms associated with adiposity contribute to the risk of joint replacement, with stronger evidence at the knee rather than the hip. © 2009 Wang et al.; licensee BioMed Central Ltd.Yuanyuan Wang, Julie Anne Simpson, Anita E Wluka, Andrew J Teichtahl, Dallas R English, Graham G Giles, Stephen Graves and Flavia M Cicuttin

Early Purchaser Involvement in Open Innovation- the case of an advanced purchasing function triggering the absorption of external knowledge in the French automotive industry

International audienceThis paper investigates the mechanisms that trigger the absorption of external knowledge in an innovative French automotive firm. An ethnographic-inspired study conducted by an academic embedded within the Innovation Purchasing Department has enable us to present a rare and new function of Purchasing that plays an important role between potential new suppliers and Research and Development personnel

The Iowa Homemaker vol.21, no.7

Spreads, Marijean Feik, page 1 Exam Checks on Seniors, Ann Koebel, page 2 Home Demonstration Proves Its Worth, Marghetta Jebson, page 3 Knit and Save, Catherine Tidemanson, page 4 Skills Enter Free Lancing, Doris McCray, page 5 What’s New in Home Economics, Dorothy Olson, page 6 Midseason Sparkle for Sally, Pauline McMahon, page 8 Departmental Highlights, Lila Williamson, page 10 Visual Education Gains Scope, Betty Ann Iverson, page 12 Ingenuity Saves Cosmetics, Betty Roth, page 13 Across Alumnae Desks, Marjorie Thomas, page 14 Bookmarks, Julie Wendel, page 15 Women’s Day, Margaret Anne Clark, page 16 Alums in the News, Bette Simpson, page 1

The Iowa Homemaker vol.22, no.2

Keeping Up With Today, Barbara Sgarlata, page 4 Women Score Dating, Julie Wendel, page 5 The Union Feeds the Navy, Betty Ann Iverson, page 6 Glass in Uniform, Dorothy Walker, page 7 Sugar Problem – A Challenge, Anne Koebel, page 8 Enter: Variety in Army Menus, Mary Schmidt, page 10 “Is It All Wool?”, Margaret Anne Clark, page 11 America Conserves Equpment, Bette Simpson, page 12 Morale on a Budget, Pat Hayes, page 14 What’s New in Home Economics, Ruth Vogel, page 16 Bookmarks, Eileen Dudgeon, page 18 Isabelle Bevier - Pioneer, Dorothy Ann Olson, page 20 Alums in the News, Harriet Zook, page 22 Our Part in the War, Virginia Bates, page 23 Iowa Goes “All Out”, Catherine Tidemanson, page 24 Tim Must S-t-r-e-t-c-h, Doris Plagge, page 26 Vanilla Joins Shortage Ranks, Grace Brown, page 28 Her Champion Pie, Pat Galligan, page 29 Across Alumnae Desks, Mary Ellen Sullivan, page 30 Speaking of Veishea, Trymby Calhoun, page 3

Meat consumption and risk of primary hip and knee joint replacement due to osteoarthritis: a prospective cohort study

Extent: 10p.Background: There is emerging evidence for a beneficial effect of meat consumption on the musculoskeletal system. However, whether it affects the risk of knee and hip osteoarthritis is unknown. We performed a prospective cohort study to examine the relationship between meat consumption and risk of primary hip and knee replacement for osteoarthritis. Methods: Eligible 35,331 participants were selected from the Melbourne Collaborative Cohort Study recruited during 1990-1994. Consumption of fresh red meat, processed meat, chicken, and fish was assessed using a food frequency questionnaire. Primary hip and knee replacement for osteoarthritis during 2001-2005 was determined by linking the cohort records to the Australian National Joint Replacement Registry. Results: There was a negative dose-response relationship between fresh red meat consumption and the risk of hip replacement (hazard ratio (HR) 0.94 per increase in intake of one time/week, 95% confidence interval (CI) 0.89-0.98). In contrast, there was no association with knee replacement risk (HR 0.98, 95% CI 0.94-1.02). Consumption of processed meat, chicken and fish were not associated with risk of hip or knee replacement. Conclusion: A high level consumption of fresh red meat was associated with a decreased risk of hip, but not knee, joint replacement for osteoarthritis. One possible mechanism to explain these differential associations may be via an effect of meat intake on bone strength and hip shape. Further confirmatory studies are warranted.Yuanyuan Wang, Julie Anne Simpson, Anita E Wluka, Dallas R English, Graham G Giles, Stephen Graves, Flavia M Cicuttin

The Iowa Homemaker vol.21, no.5

Candles Spread Christmas Cheer, Mary Ellen Sullivan, page 2 Milk Strengthens Defense, Betty Ann Iverson, page 3 American Wares Set Nation’s Tables, Ann Koebel, page 4 New World Harbours Refugees, Dorothy Ann Klein, page 5 Sally Anticipates a Gala Season, Mary Lou Springer, page 6 Applied Art Highlights, Lila Williamson, page 8 Bookmarks, Julie Wendel, page 9 What’s New in Home Economics, Dorothy Olson, page 10 For Holiday Shoppers, Betty Roth, page 12 Residence Halls Honor Women Leaders, Dorothy Gross, page 13 Express Ingenuity in Greetings, Doris Plagge, page 14 Alums in the News, Bette Simpson, page 15 Fruit Cakes for Holidays, Margaret Anne Clark, page 16 Across Alumnae Desks, Marjorie Thomas, page 18 Journalistic Spindles, Florence Byrnes, page 2

Adolescents’ interactive electronic device use, sleep and mental health: a systematic review of prospective studies

Optimal sleep, both in terms of duration and quality, is important for adolescent health. However, young people's sleeping habits have worsened over recent years. Access to and use of interactive electronic devices (e.g., smartphones, tablets, portable gaming devices) and social media have become deep-rooted elements of adolescents’ lives and are associated with poor sleep. Additionally, there is evidence of increases in poor mental health and well-being disorders in adolescents; further linked to poor sleep. This review aimed to summarise the longitudinal and experimental evidence of the impact of device use on adolescents’ sleep and subsequent mental health. Nine electronic bibliographical databases were searched for this narrative systematic review in October 2022. Of 5779 identified unique records, 28 studies were selected for inclusion. A total of 26 studies examined the direct link between device use and sleep outcomes, and four reported the indirect link between device use and mental health, with sleep as a mediator. The methodological quality of the studies was generally poor. Results demonstrated that adverse implications of device use (i.e., overuse, problematic use, telepressure, and cyber-victimisation) impacted sleep quality and duration; however, relationships with other types of device use were unclear. A small but consistent body of evidence showed sleep mediates the relationship between device use and mental health and well-being in adolescents. Increasing our understanding of the complexities of device use, sleep, and mental health in adolescents are important contributions to the development of future interventions and guidelines to prevent or increase resilience to cyber-bullying and ensure adequate sleep