Stephen P. Glasser, MD
Serum dioxin concentrations and risk of uterine leiomyoma in the Seveso W omens Health Study diabète yeux symptomes buy pioglitazone with visa. Serum dioxin concentrations and bone density and structure in the Seveso W omens Health Study diabetes prevention control alliance purchase cheap pioglitazone on-line. Behavioral changes in rats fed a diet containing 2 diabetes mellitus type 2 fatigue purchase pioglitazone without prescription,4-dichlorophenoxyacetic butyl ester metabolic disease diabetes purchase pioglitazone visa. Altered behavioral responses in 2,4-dichlorophenoxyacetic acid treated and amphetamine challenged rats. Royal Commission on the Use and Effect of Chemical Agents on Australian Person nel in Vietnam: Final report. Secretariat for the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade. Combat experience and postservice psychosocial status as predictors of suicide in Vietnam veterans. Pesticide use and menstrual cycle characteristics among premenopausal women in the Agricultural Health Study. Polychlorinated dibenzo-p-dioxins and dibenzofurans in the air of Seveso, Italy, 26 years after the explosion. Aryl hydrocarbon receptor-dependent cell cycle arrest in isolated mouse oval cells. Immunological changes among farmers exposed to phenoxy herbicides: Preliminary observations. Paternal occupation and neural tube defects: A case-control study based on the Oxford Record Linkage Study register. Risk of central nervous system tumors in chil dren related to parental occupational pesticide exposures in three European case-control studies. Effects of in vivo exposure to polyfuorinated dibenzo-p-dioxins on organo-somatic indices and ethoxyresorufn-o-deethylase activity in mice (mus musculus). Endocrine-disrupting compounds and mammary gland development: Early expo sure and later life consequences. A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain. Aryl-hydrocarbon receptor-defcient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin induced toxicity. Reproductive behaviour and consistent patterns of abnormality in off spring of Vietnam veterans. Increased lymphocyte replicatice index following 2,4-dichlorophenoxyacetic acid herbicide exposure. Presence and func tional activity of the aryl hydrocarbon receptor in isolated murine cerebral vascular endothelial cells and astrocytes. Relationship between clinical and electrophysiological fndings and indicators of heavy exposure to 2,3,7,8-tetrachlo rodibenzodioxin. An evaluation of reports of dioxin exposure and soft tissue sarcoma pathology among chemical workers in the United States. Occupational factors and risk of Parkinsons disease: A population-based case-control study. Carcinogenic risk of retained arsenic after successful treatment of acute promyelocytic leukemia with arsenic trioxide: A cause for concern Submitted by the Veterans Administration to the Committee on Veterans Affairs, U. Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice. Analyses of exposure to polychlorinated dibenzo-p-dioxins, furans, and hexachlorocyclohexane and different health outcomes in a cohort of former herbicide producing workers in Hamburg, Germany. Elimina tion of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons. Cancer risk and parental pesticide application in children of Agricultural Health Study partici pants. M ortal ity of Australian veterans of the Vietnam confict and the period and location of their Vietnam service. Relative potency for altered humoral immunity induced by polybro minated and polychlorinated dioxins/furans in female B6C3F1/N mice. Occupational exposure to n-nitrosamines and pesticides and risk of pancreatic cancer. M olecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. Prevalence of adult onset multi factorial disease among offspring of atomic bomb survivors. Dioxins released from incineration plants and mor tality from major diseases: An analysis of statistical data by municipalities. Assessment of genome damage in a population of Croatian workers employed in pesticide production by chromosomal aberration analyis, micronucleus assay and Comet assay. Study of tyrosine hydroxylase immunoreactive neurons in neonate rats lactationally exposed to 2,4-dichlorophenoxyacetic acid. Dopamine-beta hydroxylase immunohistochemical study in the locus coeruleus of neonate rats exposed to 2,4-dichlorophenoxyacetic acid through mothers milk. Results of case-control study of leukaemia and lymphoma among young people near Sellafeld nuclear plant in W est Cumbria. Effects of persistent organic pollutants on the developing respiratory and immune systems: A systematic review. Environmental pesticide exposure as a risk factor for Alzheimers disease: A case-control study. Corvallis: National Pesticide Information Center, Oregon State University Extension Services. Multiple myeloma and occupational exposures: A population-based case-control study. A population-based case-control study of urinary arsenic species and squamous cell carcinoma in New Hampshire. Human papillomavirus and diseases of the upper airway: Head and neck cancer and respiratory papillomatosis. Assessing exposure to allied ground troops in the Vietnam War: A quantitative evaluation of the Stellman exposure opportu nity index model. Exposure estimates in epidemiologic studies of Korean veterans of the Vietnam W ar. Effect of dioxin and 17estradiol on the expression of cytochrome P450 1A1 gene via an estrogen receptor depen-dent pathway in cellular and xenografted models. Association of common varients in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma. Hypothyroidism and pesticide use among male private pesticide applicators in the Agricultural Health Study. Occupational and environmental risk factors of adult primary brain cancers: A systematic review. Final report: A case-control mortality study on the association of soft tissue sarcomas, non-Hodgkins lymphomas, and other selected cancers and Vietnam military service in Pennsylvania males.
The intellectual property system diabetes epidemic purchase pioglitazone in india, notably patents diabetes in dogs glucose levels buy pioglitazone 30 mg fast delivery, also Although examples exist of suppliers that brazenly cheat by tries to address this shortcoming by giving innovators providing substandard medicines diabetes mellitus type 2 epidemiology in the philippines order 30mg pioglitazone fast delivery, for example diabetes drugs generic 30mg pioglitazone with visa, the long a time-limited monopoly in exchange for revealing the term interests of private providers do not encourage engag nature of their invention. As long as there is the prospect higher prices and suboptimal use in the short run, but the of a continued, proftable relationship with a purchaser, the intended trade-of (not always realized) is that this system supplier has an incentive to retain customers by providing produces a greater rate of innovation in the long run. The main In most countries, patents are now granted for twenty arguments have centered on the price at which they sell years, although the efective patent period of medicines is their products, particularly in poorer countries, and their eight to fourteen years, because of the time development lack of involvement in the development of new medicines takes. Afer the patent on a medicine expires, generic sup for some diseases that are major causes of morbidity and pliers are able to compete, and prices typically plummet to mortality in those countries (Trouiller et al. For the help of intense lobbying from advocacy groups, how both patented and generic products, the pharmaceutical ever, the pharmaceutical industry appears to be recognizing marketplace is also distorted by the presence of public and its wider global responsibilities and is addressing its dam private insurance. In theory, many pharmaceutical sup intervention is the rule rather than the exception, especially pliers will be quite happy to sell medicines at diferential in rich countries. The theoretically competitive model of (lower) prices in poor countries, as long as those prices are multiple suppliers and multiple purchasers is ofen replaced above their marginal costs of production and distribution by a more pragmatic model of multiple monopolistic suppli and prohibitions against reexporting to higher-priced mar ers of products and one or a few large purchasers (govern kets (parallel trade) are enforceable (Danzon and Towse ment or nongovernmental organizations) who can exercise 2003). This subject is discussed efciently as possible, using the least-cost combination of in more detail in the chapter on medicine pricing (Chapter inputs. Products that have been the subject of diferential pricing efciency gains because of the size and diversity of its opera include contraceptives, vaccines, and antiretroviral medi tions. For example, In addition, nonproft organizations are developing new a plant that produces 4 million tablets a day is likely to do so medicines for conditions such as tuberculosis, malaria, at a lower cost per tablet than one that produces only 10,000 leishmaniasis, and trypanosomiasis. Economies of scope result when initiatives are public/private-sector partnerships, involving combining a number of diferent activities enables them to pharmaceutical manufacturers (see Chapter 3 on intellec be done at lower average cost. The result has been may beneft from economies of scope by combining the considerable blurring of the traditional barriers between delivery of pharmaceuticals with the delivery of other goods the public and private sectors in pharmaceutical research, and services. Governments are in the best position to correct these inequities, and access to essential medicines is Governments interact with the private sector in many dif now regarded by some as a human right. In its simplest form, this interaction consists sector decision making is driven more by proft than by of government purchases of pharmaceuticals and supplies equity considerations, equity is ofen the frst motivation for from private pharmaceutical companies. This probability is especially high in remote areas, Market failure where cash incomes are usually lower and delivery costs higher. Tese aims can be advanced by various agents, do not face the social costs of their decisions to types of legislation; in addition, governments can infu use health care. This information asymmetry can work to the ments use to ensure that private-sector actions are consis beneft of sellers. With pharmaceuticals, the instruments used to regulate Patients inability to assess the quality, safety, or efcacy of the private sector (for example, manufacturers, distribu pharmaceuticals means they must rely on the clinicians who tors, pharmacies) include controls on medicine and service prescribe them, on pharmaceutical producers to maintain quality through mandatory inspection programs; controls production quality standards, and on governments to inter on imports (restricting imports of dangerous products or vene with regulatory activities. Inspection of medicines, permitting the import of only essential medicines); and registration and licensing of pharmacists, and medicine registration and licensure of pharmacists. Restrictions have registration processes are all ways in which governments also been widely imposed on the prices at which pharma attempt to protect consumers from dangerous, inefective, ceuticals can be sold. For example, in Australia, a section and poor-quality medicines (see Chapters 6 and 19). Tese of the National Health Act prevents the national medi demanding safety standards, although necessary, make cines selection body (the Pharmaceutical Benefts Advisory entering the market difcult for new companies. Committee) from listing a new product on the schedule at Achieving economic efciency in the presence of market a higher price than the comparators unless it ofers better failure is one of the principal aims of pharmaco-economics; efcacy or safety (see Country Study 10-1). Efciency in pharmaceutical management requires the potential efect of regulation: the extent of coverage that the medicines are efective and afordable, represent (for example, does it include both public and private sec value for money, and are used appropriately. Most also try the extent of enforcement and exemptions, and the extent to to achieve a degree of equity in the distribution of funds and which the private sector can circumvent or evade regulations services. Lack of access to essential medicines discriminates (for example, through the emergence of an uncontrolled against those with the least ability to pay, leading to avoid parallel market for nonessential or banned medicines). However, munity, its efcacy and safety compared to other medi pressures on the system are real; for example, patient cines or treatments for the condition, and, since 1993, its advocacy groups with particular clinical needs continue cost-efectiveness. In addition, the committee considers to seek relaxation of decision-making criteria that afect the fnancial implications of adding the medicine to the them. Prescribers ofen ignore restric Incremental cost-efectiveness ratios for the new medi tions, and the use of new medicines for indications and cine compared to existing medicines are then developed. The processes have been made in the technical aspects of the conduct of survived multiple technical and ethical challenges, nota pharmaco-economic analyses, progress on managing bly but not exclusively from industry. Finally, lack of good governance and corruption can be Legislation designed to improve the afordability of medi revealed in self-interested manipulation of the medicine cines is harder to implement when the government does not selection process, corruption in the award of tenders, nep subsidize medicines and thus is unable to use its extensive otism in the appointment of key staf, sales of medicines purchasing powers. For example, since 1997, South Africa on the outside by health staf, and other destructive prac has tried to regulate medicine prices in the private sector, tices. Indeed, the World Bank has identifed corruption as but it has met stif resistance from stakeholders, including one of the greatest obstacles to a countrys economic and pharmaceutical manufacturers, wholesalers, and retail phar social development (see. Whereas efectiveness con cerns the degree to which services are provided or outputs Challenges to government interventions are produced (for example, how well does a medicine work in practice In this feld, efciency is usually referred to as cost private market may fail, but government intervention also efectiveness (Drummond et al. Governments in all countries at all levels Several types of efciency concepts exist, with a variety of development are subject to threats to their efectiveness. Generally, economic efciency refers to economic sys medicines programs must acknowledge the sources of gov tems that can provide more goods and services to society ernment inefectiveness, including inefciency in service without using more resources. Scale efciency occurs when delivery, inequities in revenue collection, interest-group the production costs are reduced because of higher produc pressures, lack of good governance, and widespread corrup tion volume. Because types of efciency individual incentives for good performance, bureaucratic relate to the pharmaceutical sector, this chapter takes a infexibility, and political pressure to create employment. Allocative efciency maceuticals, for example, could result in having idle staf is the broad concept of undertaking the best combination who are unable to meet the needs of patients. Inefciencies of activities to achieve the greatest net beneft to the com in government accounting systems that cause lengthy delays munity; for example, should we spend money on prevent in payments may result in suppliers raising their prices or ing cardiovascular deaths or childhood illness Technical efciency Inequities in revenue collection can result in a reduc is concerned with determining the right quantities of difer tion in health services, which is felt most acutely by lower ent inputs and the least-expensive combination of inputs to income groups, which are most dependent on them. If achieve a given outcome; for example, what is the most cost the more afuent members of society succeed in avoiding efective way to reduce cardiovascular deaths The concepts taxes and other government levies, the fnancial burden for of allocative and technical efciency are closely linked and government activity falls on those with fewer means and in real life cannot be separated. Even honest, well-meaning politicians and ofcials are Allocative efficiency subject to interest-group pressures. Political supporters, members of the same ethnic group, and concerned business Allocative efciency has relevance to pharmaceuticals, not organizations can infuence bureaucrats to allocate services least because medicines can consume 25 to 65 percent of and resources in ways that do not promote equity. In some countries, 20 to 30 percent of pharmaceuti antibiotics is inefcient, because the same outcome could be cal expenditure is for products that have no relevance to the achieved using fewer. Polypharmacy leads to lower rates of adherence Decisions afecting allocative efciency are most ofen to treatment and is inefcient; resources are consumed, but made at the policy level, for example, deciding whether the desired clinical outcome is not achieved. For example, program man decisions involve how much to spend on primary, second agers may not have control over the allocation of funds ary, and tertiary care or whether to spend additional pro among diferent line items, such as personnel and fuel, gram funds on controlling tuberculosis or treating sexually making it difcult to use inputs in the most efcient combi transmitted infections. Incentives and management structures are impor unintended and undesirable efects; a decision to reduce tant. If a more efcient use of resources leads to tangible spending on pharmaceuticals and supplies in order to pay benefts for health workers, they are more likely to make salaries could lead to inefciency if staf are then underused more efcient choices. If they are penalized (for example, because of other shortages (for example, a surgeon who can if underspending a budget leads to less money being allo not perform operations because the operating-room equip cated next year with no ofsetting incentives), health work ment has not been maintained or because anesthetics are in ers are unlikely to behave in an efcient and cost-saving short supply). Information is important in increasing technical ef Technical efficiency ciency: managers and health care providers who have information about the costs of alternatives are more likely Technical efciency means obtaining the maximum physi to make efcient use of their resources than those who do cal output from the physical inputs in pursuit of a particular not. Technical efciency includes have been developed using information that should be avail not only the cost-efectiveness of the medicines, but also the able to most supply system managers; such indicators can be system that selects, procures, distributes, and dispenses the used to monitor supply system efciency on a routine basis medicines to consumers. Selection of medicines should consider the medicines Health care decision makers can use information on ef comparative efcacy and cost-efectiveness, measured in ciency to improve the current situation and make better terms of the money spent in achieving an adequate and sus plans related to performance, costs, and staf utilization. In addition, efciency is an important economic concept In procurement, the use of competitive international because demonstrating that existing resources are being tendering has advantages. As discussed in Chapter 9 on used efciently provides powerful support to requests for medicine pricing, improving the efciency of the ten additional resources. Order cheap pioglitazone on-line. JDRF: Walk.
Syndromes
|
