Cyrus Cooper

Bio: Cyrus Cooper is an academic researcher from Southampton General Hospital. The author has contributed to research in topics: Population & Osteoporosis. The author has an hindex of 204, co-authored 1869 publications receiving 206782 citations. Previous affiliations of Cyrus Cooper include University of Oxford & University of York.

Partial adherence: a new perspective on health economic assessment in osteoporosis

Abstract: Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit. A number of economic models have been developed to evaluate osteoporosis therapies and support decisions regarding efficient allocation of health care resources. Adherence to treatment is seldom incorporated in these models, which may reduce their validity for decision-making since adherence is poor in real-world clinical practice. An ad hoc working group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review key issues concerning the incorporation of partial adherence in health economic models. Observational data have shown that poor adherence is associated with an increase in the risk for fragility fracture. Health economic modelling indicates that full adherence is associated with more quality-adjusted life years gained than partial adherence, as well as higher treatment costs and lower fracture-related costs. Although adherence appears as an important driver of cost-effectiveness, the effect is dependent on a range of other variables, such as offset time, fraction of benefit, fracture risk, fracture efficacy, fracture-related costs, and drug cost, some of which are poorly defined. Current models used to evaluate cost-effectiveness in osteoporosis may oversimplify the contributions of compliance and persistence. Partial adherence has a significant impact on cost-effectiveness. Further research is required to optimise thresholds of compliance and persistence, the impact of gap length, offset times, and fraction of benefit.

Maternal vitamin D supplementation during pregnancy.

Abstract: The classical role of vitamin D is in calcium and phosphate homeostasis, and it is widely known that that severe vitamin D deficiency (VDD) can result in rickets, osteomalacia and neonatal hypocalcaemia. Clinically, neonatal hypocalcaemia can result in seizures, and has been associated with softening and thinning of the skull (craniotabes) 4, and rarely, dilated cardiomyopathy 5. However, there is increasing evidence to suggest that VDD in pregnancy is associated with wide ranging clinical outcomes, including obstetric complications, preterm birth, and adverse offspring outcomes affecting the skeletal, immune, and respiratory systems6. As a result, a number of national and international guidelines recommend vitamin D supplementation during pregnancy or offer guidance on defining deficiency and sufficiency (Table 1), though there is considerable debate regarding the thresholds for vitamin D deficiency and sufficiency. Most recommend between 400 and 600 IU (10-15 micrograms) cholecalciferol daily throughout pregnancy, although this is not currently supported by the World Health Organisation (WHO)7. It is important to mention that the Endocrine Society recommends a safe upper limit for 25(OH)D intake in pregnancy of 10,000 IU/day for individuals over the age of 19 years at risk of vitamin D deficiency, though their recommendations for those not at risk remain at 600IU/day8. Guideline Countries covered by recommendation Deficiency (nmol/l) Insufficiency (nmol/l) Sufficiency (nmol/l) Dietary recommendation for vitamin D intake in pregnancy (IU)* - RI + Scientific Advisory Committee on Nutrition (SACN)9 and UK Department for Health UK <25 ≥25 400 Institute of Medicine (IOM) 10 USA and Canada < 30 30-50 ≥ 50 600 Endocrine Society Practice Guidelines 11 Worldwide < 50 50-75 ≥ 75 600 British Paediatric and Adolescent Bone Group 12 UK < 25 25-50 ≥ 50 Refers to SACN, 400 Global Consensus Recommendations on Prevention and Management of Nutritional Rickets 13 Worldwide < 30 30-50 ≥ 50 600 National Osteoporosis Society (UK) 14 UK < 30 30-50 ≥ 50 No recommendation Canadian Paediatric Society 15 Canada < 25 25-75 75-225 No recommendation Working group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia 16 Australia and New Zealand < 50 ≥ 50 At the end of winter (level may need to be 10-20 nmol/l higher at the end of summer) No recommendation NORDEN Nordic Nutrition Recommendations 17 Nordic countries <30 ≥ 50 400 European Food Safety Authority 18 EU countries < 50 ≥ 50 600 Open in a separate window * 400 IU cholecalciferol equivalent to 10 micrograms, +RI – Recommended Intake in low-risk individuals

Secular trends in the incidence of postmenopausal vertebral fractures.

Abstract: Several studies suggest secular increases in hip fracture incidence through this century, but little is known about such trends for vertebral fracture. We have examined changes in the incidence of clinically ascertained vertebral fractures among Rochester, Minnesota residents aged 35-69 years, that were first diagnosed between 1950 and 1989. Our results indicate no overall increase in incidence over the 40-year period. Categorization of fractures according to the level of preceding trauma, however, revealed a significant increase in the incidence of fractures following moderate trauma among women aged 60-69 years. This increase occurred between 1950 and 1964, and leveled off thereafter. Rates for severe trauma fractures among postmenopausal women, and for vertebral fractures from any cause among younger men and women, remained stable. The rise in moderate trauma fractures in postmenopausal women paralleled that for hip fractures in Rochester and began to plateau at around the same time. It might have resulted from increased diagnosis of vertebral fractures, but the increase in hip fracture incidence is inconsistent with this explanation. An increase in the prevalence of osteoporosis, however, might account for the trend in both types of fractures.

Developmental Influences, Muscle Morphology, and Sarcopenia in Community-Dwelling Older Men

Abstract: Background. Sarcopenia is associated with disability, morbidity, and mortality. Lower birth weight is associated with reduced muscle mass and strength in older people, suggesting that developmental influences are important in sarcopenia. However, underlying mechanisms are unknown. Our objective was to determine whether low birth weight is associated with altered skeletal muscle morphology in older men. Methods. Ninety-nine men with historical records of birth weight (≤3.18 kg and ≥3.63 kg), aged 68–76 years, consented for detailed characterization of muscle, including a biopsy of the vastus lateralis. Tissue was processed for immunohistochemical studies and analyzed to determine myofibre density, area, and score. Results. Muscle fibre score (fibres kilograms per square millimeter ) was significantly reduced in those with lower birth weight: 1.5 × 10 3 vs 1.7 × 10 3 , p = .04 unadjusted; p = .09 adjusted for age, height, and physical activity. In addition, there was a trend for reduced myofibre density (fibres per square millimeter ) in those with lower birth weight: total fibre density: 176 vs 184, type I myofibre density: 77 vs 80, and type II myofibre density: 99 vs 105. Types I and II myofibre areas (square micrometers) were larger in those with lower birth weight: type I: 4903 vs 4643 and type II: 4046 vs 3859. However, none of these differences were statistically significant. Conclusions. This is the first study showing that lower birth weight is associated with a significant decrease in muscle fibre score, suggesting that developmental influences on muscle morphology may explain the widely reported associa tions between lower birth weight and sarcopenia. However, the study may have been underpowered and did not include women supporting replication in larger cohorts of older men and women.

Risk of fractures in patients with multiple sclerosis: A population-based cohort study

Abstract: Objective: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. Methods: A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998–2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. Results: During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18–2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21–7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77–5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06–5.63]) in the previous 6 months, compared with controls. Conclusions: Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Using Multivariate Statistics

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Vitamin D Deficiency

Abstract: Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.