13856154
Macroeconomic impact of pandemic influenza and associated policies in Thailand, South Africa and Uganda
BACKGROUND
Research has shown the value of conducting a macroeconomic analysis of the impact of influenza pandemics. However, previous modelling applications focus on high-income countries, and there is a lack of evidence concerning the potential impact of an influenza pandemic on lower- and middle-income countries.


OBJECTIVES
To estimate the macroeconomic impact of pandemic influenza in Thailand, South Africa and Uganda with particular reference to pandemic (H1N1) 2009.


METHODS
A single-country whole-economy Computable General Equilibrium (CGE) model was set up for each of the three countries in question and used to estimate the economic impact of declines in labour attributable to morbidity, mortality and school closure.


RESULTS
Overall GDP impacts were less than 1% of GDP for all countries and scenarios. Uganda's losses were proportionally larger than those of Thailand and South Africa. Labour-intensive sectors suffer the largest losses.


CONCLUSION
The economic cost of unavoidable absence in the event of an influenza pandemic could be proportionally larger for low-income countries. The cost of mild pandemics, such as pandemic (H1N1) 2009, appears to be small, but could increase for more severe pandemics and/or pandemics with greater behavioural change and avoidable absence.
20390905
Use, option and externality values: are contingent valuation studies in health care mis-specified?
A general population sample of Australian respondents completed a contingent valuation (CV) survey that asked them to value six scenarios. These varied according to whether the scenario was seeking to elicit: (i) use value; (ii) externality value; (iii) option value; or (iv) a combination. Results indicate that use plus externality and/or option value was significantly greater than use value alone. As CV studies in health (care) overwhelmingly focus on use value alone - often implicitly through study design rather than explicitly - this raises the possibility of mis-specification in CV research in health (care). The implications for CV in health (care) are considered.
23464544
A macroeconomic approach to evaluating policies to contain antimicrobial resistance
BackgroundAntimicrobial resistance (AMR) is, at least in part, associated with high antimicrobial usage and causes increased morbidity, mortality and healthcare costs. However, policies to contain AMR focus on ‘micro’ interventions — typically in one institution (usually a hospital). Furthermore, in evaluating these interventions, economists tend to concentrate on the economic impact to the healthcare sector alone, which may give an incorrect estimation of the social costs and benefits of a disease or intervention.MethodsThis study outlines and illustrates a macroeconomic approach to tackling AMR through the evaluation of three ‘macro’ policies: regulation, permits and taxes/charges. In addition to effects on the healthcare sector, the effect of AMR (and these three policies to contain it) on labour productivity, GDP, household income, government transfers, tax revenues, unemployment, inflation and social services are estimated for the UK using the specific context of methicillin-resistant Staphylococcus aureus (MRSA).ResultsAMR is likely to have a far greater impact on the national economy than would be estimated by concentrating on the healthcare sector alone.ConclusionThe permit system appears to offer the most efficient ‘solution’ to optimising antimicrobial consumption and, hence, reducing the development of resistance.
11081915
Estimating the economic impact of pandemic influenza: An application of the computable general equilibrium model to the UK

 Abstract
 
 There is concern regarding the impact that a global infectious disease pandemic might have, especially the economic impact in the current financial climate. However, preparedness planning concentrates more upon population health and maintaining a functioning health sector than on the wider economic impact. We developed a single country Computable General Equilibrium model to estimate the economic impact of pandemic influenza (PI) and associated policies. While the context for this development was the United Kingdom, there are lessons to be drawn for application of this methodology, as well as indicative results, to other contexts.
 Disease scenarios were constructed from an epidemiological model which estimated case fatality rates (mild, moderate and severe) as 0.06%, 0.18% and 0.35%. A clinical attack rate of 35% was also used to produce influenza scenarios, together with preparedness policies, including antivirals and school closure, and the possible prophylactic absence of workers.
 UK cost estimates (in Sterling) are presented, together with relative percentage impacts applicable to similar large economies. Percentage/cost estimates suggest PI would reduce GDP by 0.3% (£3.5bn), 0.4% (£5bn) and 0.6% (£7.4bn) respectively for the three disease scenarios. However, the impact of PI itself is smaller than disease mitigation policies: combining school closure with prophylactic absenteeism yields percentage/cost effects of 1.1% (£14.7bn), 1.3% (£16.3bn) and 1.4% (£18.5bn) respectively for the three scenarios. Sensitivity analysis shows little variability with changes in disease parameters but notable changes with variations in school closure and prophylactic absenteeism. The most severe sensitivity scenario results in a 2.9% (£37.4bn), 3.2% (£41.4bn) and 3.7% (£47.5bn) loss to GDP respectively for the three scenarios.
 

11455466
Trade and health: an agenda for action
The processes of contemporary globalisation are creating ever-closer ties between individuals and populations across different countries. The health of a population, and the systems in place to deliver health care, are affected increasingly by factors beyond the population and health system. The Lancet's Series on trade and health has provided an overview of these links between international trade, trade liberalisation, and health, and raised the key issues that face the health community. In this final paper in the Series, we call for a substantial and sustained effort by those within the health profession to engage with issues of trade, to strengthen institutional capacity in this area, and to place health higher on the agenda of trade negotiations. The rapid rise of trade agreements and treaties, as well as trade that occurs beyond these institutional boundaries, means that further action is required by a range of actors, including WHO, the World Bank, the World Trade Organization (WTO), regional agencies, foundations, national governments, civil society, non-governmental organisations, and academics. The stewardship of a domestic health system in the 21st century requires a sophisticated understanding of how trade affects, and will affect, a country's health system and policy, to optimise opportunities to benefit health and health care while minimising the risks posed though the assertion of health goals in trade policy. To acheive this will place a premium on all those engaged in health to understand the importance of trade and to engage with their counterparts involved in trade and trade policy. We hope that this Series has prompted the reader to become involved in these efforts.
45471144
Trade and public health: facing the challenges of globalisation
It is vital that public health professionals engage with issues concerning trade organisations and treaties.
23578107
Synaptic dysfunction in Huntington’s disease: a new perspective
Abstract.Huntington’s disease (HD) is caused by a polyglutamine expansion in the protein huntingtin and is characterized by intraneuronal inclusions and widespread neuronal death at the late stage of the disease. In research, most of the emphasis has been on understanding the cell death and its mechanisms. Until recently, it was believed that the vast majority, if not all, of the symptoms in HD are a direct consequence of neurodegeneration. However, increasing evidence shows that subtle alterations in synaptic function could underlie the early symptoms. It is of particular interest to understand the nature of this neuronal dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This review describes recent advances in understanding synaptic dysfunction in HD.
21083531
Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M.
Legumain, an asparaginyl endopeptidase, is up-regulated in tumour and tumour-associated cells, and is linked to the processing of cathepsin B, L, and proMMP-2. Although legumain is mainly localized to the endosomal/lysosomal compartments, legumain has been reported to be localized extracellularly in the tumour microenvironment and associated with extracellular matrix and cell surfaces. The most potent endogenous inhibitor of legumain is cystatin E/M, which is a secreted protein synthesised with an export signal. Therefore, we investigated the cellular interplay between legumain and cystatin E/M. As a cell model, HEK293 cells were transfected with legumain cDNA, cystatin E/M cDNA, or both, and over-expressing monoclonal cell lines were selected (termed M38L, M4C, and M3CL, respectively). Secretion of prolegumain from M38L cells was inhibited by treatment with brefeldin A, whereas bafilomycin A1 enhanced the secretion. Cellular processing of prolegumain to the 46 and 36 kDa enzymatically active forms was reduced by treatment with either substance alone. M38L cells showed increased, but M4C cells decreased, cathepsin L processing suggesting a crucial involvement of legumain activity. Furthermore, we observed internalization of cystatin E/M and subsequently decreased intracellular legumain activity. Also, prolegumain was shown to internalize followed by increased intracellular legumain processing and activation. In addition, in M4C cells incomplete processing of the internalized prolegumain was observed, as well as nuclear localized cystatin E/M. Furthermore, auto-activation of secreted prolegumain was inhibited by cystatin E/M, which for the first time shows a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity.
33674054
Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.
BACKGROUND
Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified.


METHODS
Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures.


RESULTS
Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13).


CONCLUSION
Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.
29843044
Hormone trajectories leading to human birth
The mechanisms regulating human parturition and labor remain unknown. This ignorance is expensive as preterm birth is responsible for 70% of neonatal mortality and 50% of cerebral palsy. Methods for the prediction of preterm birth and treatments for women in preterm labor have poor efficacy reflecting our limited knowledge of the mechanisms involved. Recent research has supported the view that parturition is a cascade of events that commences early in pregnancy and involves the mother, fetus, placenta, membranes, cervix and myometrium. Although a number of the key hormones and proteins involved have been identified, the relationships between these factors in time and tissues remain unclear. Placental production of Corticotropin-releasing hormone (CRH) is proposed as an early event regulating the cascade of events. Central to the onset of parturition will be a mechanism for progesterone withdrawal and estrogen activation in human. Two forms of progesterone receptor with opposing actions exist in the human myometrium. Progesterone receptor A (PR-A) is a dominant negative repressor of progesterone receptor B (PR-B). Preliminary studies strongly support the hypothesis that the onset of human parturition is initiated by rising concentrations of PR-A in the myometrium.
35241468
The effect of surgery on plasma beta-endorphin and methionine-enkephalin.
Seven women undergoing abdominal hysterectomy under halothane and nitrous oxide analgesia had plasma samples taken before, during and after surgery for assay of adrenocorticotrophin (ACTH), beta-endorphin, beta-lipotrophin and methionine (Met)-enkephalin immunoreactivity. Plasma ACTH, beta-endorphin and beta-lipotrophin all rose in parallel from the start of surgery and were unaffected by postoperative opiate analgesia. Plasma Met-enkephalin concentrations did not change significantly during the course of the surgery and immediate post-operative period, although the variance of the samples increased at the time of the first skin incision. These data indicate that the stress of surgery and post-operative pain, while producing marked elevations of proopiomelanocortin-derived peptides, are not associated with changes in plasma Met-enkephalin. These data exclude a role for circulating Met-enkephalin in the modulation of surgical pain but do not exclude such a role for beta-endorphin.