In Vivo Age Dependency of Unfractionated Heparin in Infants and Children

Introduction
Unfractionated Heparin (UFH) is used widely in paediatrics. Paediatric specific recommendations for UFH therapy are few, with the majority of recommendations being extrapolated from adult practice. In vitro studies have shown that this practice may be suboptimal. This study aimed to improve the understanding of the impact of age upon UFH response in vivo.

Materials and Methods
This prospective, observational study, conducted in the Paediatric Intensive Care Unit (PICU), included: patients 16 years or younger; treated with UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT, Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin Potential. Results were grouped according to patient age (i.e. < 1, 1-5, 6-10 and 11-16 years).

Results
85 patients received an equivalent mean UFH dose with a median duration of 3 days. Antithrombin levels were decreased compared to age-related norms in children up to 11 years of age. APTT results were comparable across the age-groups. The Anti-Xa results using two different assays showed a trend for lower values in younger children. All children less than one year old recorded Anti-Xa values outside the therapeutic range for heparin therapy, for both assays. There was a trend for decreased Anti-IIa activity in younger children. Endogenous Thrombin Potential showed a significant trend for increased inhibition in older children. In vitro Antithrombin supplementation did not change the Anti-Xa or thrombin generation.

Conclusions
This study confirms that, in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as the inhibition of endogenous thrombin potential is age dependent and that these differences are not purely AT dependent. The implication is that the anticoagulant and antithrombotic effect of a given dose of UFH differs with age. Clinical outcome studies to determine the optimal dosing for each age group are warranted.

Abbreviations
UFH, Unfractionated Heparin; ETP, Endogenous Thrombin Potential; AT, Antithrombin; APTT, Activated Partial Thromboplastin Time

Age dependency of intrarenal resistance index (RI) in healthy adults and patients with fatty liver disease

BACKGROUND: Our aim was to investigate the influence of age and gender on intrarenal resistance index (RI) measurements in 78 healthy subjects (46 males, 32 females; group 1) and 35 subjects (group 2) with fatty liver disease (28 males and 7 females). SUBJECTS AND METHODS: First, each subject underwent a conventional abdominal ultrasound examination. Then, intrarenal RI values were determined from three distinct interlobar and cortical arteries respectively on both kidneys. The correlation of intrarenal RI with age and gender as a variable was statistically evaluated by linear regression. RESULTS: In group 1, the variables gender, kidney region and comparison of right versus left kidney had no significant effect on intrarenal RI (p>0.05). The variable age, on the other hand, showed a significant positive correlation on all four defined measuring points (p<0.01) with linear correlation coefficients of r = 0.26 (left kidney, central) to r = 0.37 (right kidney, cortical). Therefore normal RI values at ages 25, 45, 65 years could be defined as 0.59, 0.61 and 0.63, respectively. Age dependency can thus be expressed as a function with the formula y = 0.565 + 0.001.x. Patients with fatty liver disease showed age dependency on renal RI (p<0.01) as well. CONCLUSION: In accordance with other studies, the influence of age on intrarenal RI measurement is significant in healthy subjects. Intrarenal RI values from subjects with a fatty liver disease showed age dependency as well. Therefore it is necessary to consider the age of the examined person to interpret RI values correctly.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.

Measuring Dependency Ratios using National Transfer Accounts. CEPS Working Document No. 420/April 2016

It is now widely recognised that the socio-economic changes that ageing societies will bring about are poorly captured by the traditional demographic dependency ratios (DDRs), such as the old-age dependency ratio that relates the number of people aged 65+ to the working-age population. Future older generations will have increasingly better health and are likely to work longer. By combining population projections and National Transfer Accounts (NTA) data for seven European countries, we project the quantitative impact of ageing on public finances until 2040 and compare it to projected DDRs. We then simulate the public finance impact of changes in three key indicators related to the policy responses to population ageing: net immigration, healthy ageing and longer working lives. We do this by linking age-specific public health transfers and labour market participation rates to changes in mortality. Four main findings emerge: first, the simple old-age dependency ratio overestimates the future public finance challenges faced by the countries studied – significantly so for some countries, e.g. Austria, Finland and Hungary. Second, healthy ageing has a modest effect (on public finances) except in the case of Sweden, where it is substantial. Third, the long-run effect of immigration is well captured by the simple DDR measure if immigrants are similar to the native population. Finally, increasing the length of working lives is central to addressing the public finance challenge of ageing. Extending the length of working lives by three to four years over the next 25 years – equivalent to the increase in life expectancy – severely limits the impact of ageing on public transfers.

Old age security reform in China /

Mode of access: Internet.

A functional coefficient model view of the Feldstein–Horioka puzzle

What does the saving–investment (SI) relation really measure and how should the SI relation be measured? These are two of the most discussed issues triggered by the so-called Feldstein–Horioka puzzle. Based on panel data we introduce a new variant of functional coefficient models that allows to separate long and short to medium run parameter dependence. The new modeling framework is applied to uncover the determinants of the SI relation. Macroeconomic state variables such as openness, the age dependency ratio, government current and consumption expenditures are found to affect the SI relation significantly in the long run.

Social Security in the United States: Overview and Outlook

Includes bibliography

The Canadian retirement income system

Includes bibliography

Aging and the governance of the healthcare system in Japan. Bruegel Working Paper 2014/14, December 2014

Japan is the most rapidly aging country in the world. This is evidence that the social security system, which consists of the pension system, healthcare system and other programmes, has been working well. The population is shrinking because of a falling birth rate. It is expected that the population will fall from 128 million in 2010 to 87 million in 2060. During this period, the ratio of people aged 65 or over will rise from 23 percent to 39.9 percent. Japan’s age dependency ratio was 62 in 2013, the highest among advanced nations. It is expected to rise sharply to 94 in 2050 (see Figure 1 on page 4). A total reform of the Japanese social security system, therefore, is inevitable. From the point of view of fiscal reconstruction, reform of the healthcare system is the most important issue. The biggest problem in the healthcare system is that both the funding system and the care-delivery system are extremely fragmented. The government is planning its reform of the healthcare system based on the principle of integration. Other advanced economies could learn from the Japanese experience.

The grand divergence: global and European current account surpluses. Bruegel Working Paper 2015/08, 13 August 2015

Global current account imbalances widened before the 2007/2008 crisis and have narrowed since. While the post-crisis adjustment of European current account deficits was in line with global developments (though more forceful), European current account surpluses defied global trends and increased. We use panel econometric models to analyse the determinants of medium-term current account balances. Our results confirm that higher fiscal balances, higher GDP per capita, more rapidly aging populations, larger net foreign assets, larger oil rents and better legal systems increase the medium-term current account balance, while a larger growth differential and a higher old-age dependency ratio reduce it. European current account surpluses became excessive during the past twelve years according to our estimates, while they were in line with model predictions in the preceding three decades. Generally, the gap between the actual current account and its fitted value in the model has a strong predictive power for future current account changes. Excess deficits adjust more forcefully than excess surpluses. However, in the 2004-07 period, excess imbalances were amplified, which was followed by a forceful correction in 2008-15, with the exception of European surpluses.

La implementación de la trayectoria de desarrollo sostenible por parte de los pequeños estados insulares en desarrollo del Pacífico frente a su condición de vulnerabilidad

La investigación busca determinar el propósito que persiguen los pequeños Estados insulares en desarrollo del Pacífico al adoptar una trayectoria de desarrollo sostenible. Se plantea que la adopción de una trayectoria de desarrollo sostenible es la estrategia por medio de la cual estos Estados buscan hacer frente a su condición de vulnerabilidad; lo cual logran a través del uso de la diplomacia en distintos escenarios multilaterales, con el fin de modificar tanto sus prácticas como las de otros actores.

Long-term clinical outcome after liver transplantation

With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.

Ageing, solidarity and social protection in Latin America and the Caribbean: time for progress towards equality

Includes bibliography

Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT. (Blood. 2012;120(16):3353-3359)

Age determination and Argon geochemistry of Hawaiian Emperor seamounts

The Hawaiian-Emperor bend has played a prominent yet controversial role in deciphering past Pacific plate motions and the tempo of plate motion change. New ages for volcanoes of the central and southern Emperor chain define large changes in volcanic migration rate with little associated change in the chain's trend, which suggests that the bend did not form by slowing of the Hawaiian hot spot. Initiation of the bend near Kimmei seamount about 50 million years ago (MA) was coincident with realignment of Pacific spreading centers and early magmatism in western Pacific arcs, consistent with formation of the bend by changed Pacific plate motion.